CONTENTS TITLE PAGE No ABSTRACT INTRODUCTION Buccal Drug Delivery System Advantages Delivery through Buccal Mucosa Various strategies employed for Buccal Delivery CHAPTER 2 LITERATURE REVIEW CHAPTER 3 AIM AND OBJECTIVE CHAPTER 4 PLAN OF WORK CHAPTER 5 DRUG PROFILE CHAPTER 6 EXCIPIENT PROFILE CHAPTER7 MATERIAL AND EQUIPMENTS Tl List of materials used 72 List of Equipments CHAPTER 8 METHODOLOGY CHAPTER9 RESULTS AND DISCUSSION CHAPTER 10 CONCLUSION CHAPTER 11 REFERENCESAbstract: The buccal route has a relatively robust mucosa, has the advantage of allowing excellent accessibility, and reasonable patient compliance. Within the oral mucosal cavity, the buccal region offers attractive route of administration for local or systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. Recently interest has been focused on the delivery of drug to or via mucous membrane by the use of mucoadhesive material, several mucoadhesive formulations are available under development and drug delivery via buccal mucosa is gaining importance of a novel route of drug administration. The purpose of this study was to develop and optimize formulations of mucoadhesive patches of Esomeprazole. The patches were prepared by the solvent casting method using Chitosan as basic polymer and HPMC and Eudragit L 100, Keywords: Buccal Patches, Esomeprazole, solvent casting Method, FTIR studies, In vitro drug release studies1.1 Buceal Drug Delivery System The unique environment of the oral cavity offers its potential as a site for drug delivery. Because of the rich blood supply and direct access to systemic circulation, the oral mucosal route is suitable for drugs, which are susceptible to acid hydrolysis in the stomach or which are extensively metabolized in the liver (first pass effect). The total area of the oral cavity is about 100 cm”. Out of this about one third is the buccal surface, which is lined with an epithelium of about 0.5 mm thickness. The oral mucosal surface is constantly washed by the saliva'® (daily turn out is about 0.5 to 2 liters). The continuous secretion of saliva results in rapid removal of released drug. Conversely, the thin mucin film, which exists on the surface of the oral mucosa, may provide an opportunity to retain a drug delivery system in contact with the mucosa for prolonged periods if it is designed to be mucoadhesive. Such systems ensure a close contact with absorbing membrane, thus optimizing the drug concentration gradient across the biological membrane and reducing the differential pathway. Therefore, the buccal (oral) mucosa may be a potential site for controlled or sustained drug delivery. Drug delivery via the membranes of the oral cavity is traditionally divided into three categories, © Buccal delivery, which infers drug administration through the lining of the check to the systemic circulation. ‘© Sublingual delivery, which infers drug administration through the administration of drug via membranes of the floor of the mouth for the systemic circulation. * Local delivery to mouth, which involves treatment conditions with in the oral cavity by administration to the affected mucosal tissues. These sites for delivery differ in both structure and composition as well as in degree of permeability and therefore, also vary in their ability to retain a delivery for a desired length of time.Buccal route of drug delivery is a good alternative, amongst the various routes of drug delivery. Buccal drug delivery is most advantageous because it abundant blood supply in buccal mucosa, bypassing the hepatic firstpass effect and accessibility. However, peroral administration of drugs has disadvantages such as hepatic first pass metabolism and enzymatic degradation within the Gl tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for drug administration. Oral cavity has been investigated for number of applications including the treatment of periodontal disease bacterial and fungal infection, aphthous and dental stomatitis. Over the last two decades mucoadhesion has become of interest for its systemic delivery by retaining a formulation intimate contact with buccal cavity. The term bio adhesion has been used to define the attachment of a synthetic natural macromolecule to a biological tissue for an extended period of time, When a substrate is a mucosal system adheres and interacts primarily with the mucus layer, this phenomenon being referred to as mucoadhesion. The adhesive properties of such drug delivery platforms can reduce the enzymatic degradation due to the increased intimacy between the delivery vehicle and the absorbing membrane. The use of mucoadhesive polymers in buccal drug delivery has a greater application. Various mucoadhesive devices, including tablets, films, patches, disks, strips, ointments and gels, have recently been developed. However, buccal patch offer greater flexibility and comfort than the other devices. In addition, a patch can circumvent the problem of the relatively short residence time of oral gels on mucosa, since the gels are easily washed away by saliva. Buccal route of drug delivery provides the direct access to the systemic circulation through the jugular vein bypassing the first pass hepatic metabolism leading to high bioavailability. 1.2 Advantages © Bypass of the gastrointestinal tract and hepatic portal system, increasing the bioavailability of orally administered drugs that otherwise undergo hepatic first metabolism. © Improved patient compliance due to the elimination of associated pain with injections; administration of drugs in unconscious or incapacitated patients. © Sustained drug delivery.© A relatively rapid onset of action can be achieved relative to the oral route, and the formulation can be removed if therapy is required to be discontinued. «Increased ease of drug administration 1.3 Disadvantages ¢ Limited absorption area- the total surface area of the membranes of the oral cavity available for drug absorption is 170 cm? of which ~$0 cm2 represents non-keratinized tissues, including buccal membrane. © The barriers such as saliva, mucus membrane coating granules, basement membrane ete retard the rate and extent of drug absorption through the buccal mucosa, © Continuous secretion of the saliva(0.5-2 I/day)leads to subsequent dilution of the drug. © The hazard of choking by involuntarily swallowing the delivery system is a concern. «Swallowing of saliva can also potentially lead to the loss of dissolved or suspended drug and ultimately the involuntary removal of the dosage form. 1.4 Delivery through Buccal Mucosa Administration of a drug via the buccal mucosa (the lining of the check) to the systemic circulation is defined as buccal delivery. Despite, the buccal mucosa is significantly less permeable than the sublingual mucosa and usually not able to provide rapid drug absorption or good bioavailability, it is relatively more permeable than the skin and also offers other advantage over alternative delivery routes. The fact that the buccal mucosa is less permeable than sublingual floor makes it more desirable site for sustained drug delivery Apart from avoiding enzymatic degradation and first pass metabolism, the non acidic conditions and lipophilic nature of the buccal tissue provide potential and promises for successful delivery of peptide and proteins.1.5 The various strategies Employed for Buccal Delivery “ Bioadhesive Buccal Tablets % Bioadhesive buccal Gels * Bioadhesive Buccal Patches A. Bloadhesive Buccal Tablets Bioadhesive tablets are immobilized drug delivery systems. They can be formulated into monolithic, partially coated or multi-layered matrices. Monolithic tablets are easy to manufacture by conventional techniques and provide for the possibility of loading large amount of drug. In case of bi-layered tablets, drug can be incorporated in the adhesive layer, which comes in contact with the mucosal surface. This drug containing mucoadhesive layer is then protected from the oral cavity environment by a super upper inert layer (backing layer), which faces into the oral cavity. B. Bioadhesive Buccal Patches Adhesive patches can be designed either for unidirectional release into the oral mucosa or for bi- the system can be used as drug carrier or as an adhesive for the retention of a drug loaded irectional release into the oral cavity as well as into the oral mucosa. The adhesive part of non-adhesive layer. In this respect, a peripheral adhesive ring could be casted. The use of an impermeable backing layer will maximize the drug concentration gradient and prolong adhesion because the system is protected from saliva, C. Bioadhesive buccal Gels Viscous adhesive gels have been designed for local therapy using polyacrylic acid and polymethacrylate as gel forming polymers. Gels are reported to prolong residence time on the oral mucosa to a significant level. This not only improves absorption but also allows for sustained release of the active principle. D. Semisolid Preparations (Ointment and Gels): Bioadhesive gels or ointment have less patient acceptability than solid bioadhesive dosage form, and most of the dosage forms are used only for localized drug therapy within the oral cavity.one of the original oral mucoadhesive delivery systems- “orabase”- consists of finely ground pectin, gelatin and sodium carboxy methylcellulose dispersed in a poly (ethylene) and a ground pectin, gelatin and sodium carboxy methylcellulose dispersed in poly (ethylene) and a mineral oil gel base, which can be maintained at its site of application for 15-150 minutes.E. Powders: Hydroxypropyl cellulose and beclomethasone in powder form when sprayed onto the oral mucosa of rats, a significant increase in the residence time relative to an oral solution is seen, and 2.5% of beclomethasone is retained on buccal mucosa for over 4 hours. 1.6 Structure & Design of Buccal Dosage Form: Drug delivery designed for the buccal mucosa contains a polymeric adhesive component. When in contact with the saliva, the adhesive attaches to the mucosa causing immediate and rapid drug delivery, Trans mucosal drug delivery systems can be unidirectional or bi- directional. Unidirectional patches release the drug only into the mucosa, while bi-directional patches release the drug in both the mucosa and the mouth, The buccal patch is designed in either a matrix configuration with drug, adhesive, and additives mixed together, or a reservoir system that contains a cavity for the drug and additives separate from the additives. An impermeable backing is applied to control the direction of drug delivery, to reduce patch deformation and disintegration while in the mouth; and to prevent drug loss. Additionally, the patch can be constructed to undergo minimal degradation in the mouth, or can be designed to dissolve almost immediately. Components or structural features of oral cavity:- Fig no:-1 Anatomical structure of Oral Cavity (Anterior View) Fig no:-2 structure of buccal mucosa 1.7Buccal dosage form for buccal delivery: In the past decades, to till now, different drug delivery systems intended for buccal administration have been developed. The most common buccal dosage forms are tablets and patches. Such type of form must be of a small size and a suitable geometry so as to not interfere with physiological function of the mouth, even aftertheir hydration in the oral cavity. One of the requirements is that they do not adhere too tightly because it is undesirable to exert too much force to remove the formulation/ dosage form after use, otherwise the mucosa could be injured. An alternative is the use of formulations that dissolve or disintegrate completely during the application period. Moreover, in the case of Transmucosal administration, Drug release should be unidirectional (towards the mucosa), and the release into the saliva should be avoided. 1. Matrix type: The buccal patch designed in a matrix configuration contains drug, adhesive, and additives mixed together. 2, Reservoir type: The buccal patch designed in a reservoir system contains a cavity for the drug and additives separate from the adhesive. An impermeable backing is applied to control the direction of drug delivery, to reduce patch deformation and disintegration while in the mouth and to prevent drug loss. Additionally. the patch can be constructed to undergo minimal degradation in the mouth, or can be designed to dissolve almost immediately. 18 Patches: Patches are laminated and generally consist of an impermeable backing layer and a drug-containing layer that has muco adhesive properties and from which the drug is released in a controlled manner. Moreover, buccal patches for systemic delivery of tyrotropin-releasing hormone, octreotide, oxytocin, —_buserelin, calcitonin and leuenkephalinhave been studied. 1.8.1 Novel drug delivery system: Novel drug delivery systems, such as lipophilic gel, buccal spray and phospholipids vesicles have been recently proposed to deliver peptides via the buccal route. A novel liquid aerosol formulation (Oralin, Generex Biotechnology) has been already developed. This system allows precise insulin dose delivery via a metered dose inhaler in the form of fine aerosolized droplets directed into the mouth. This oral aerosol formulation is rapidly absorbed through the buccal mucosal epithelium, and it provides the plasma insulin levels necessary to control postprandial glucose rise in diabetic patients. This novel, pain-free, oral insulin formulation has a number of advantages including rapid absorption, a simple (user-friendly) administration technique, precise dosing control (comparable to injection within one unit) and bolus delivery of drug. 1.8.2 Buccal drug delivery system: Delivery system designed to deliver drug systemically or locally via buecal mucosa, Buceal delivery refers to the drug release which can occur when a dosage form is placed in the outer vestibule between the buccal mucosa and gingival1.9 Mechanism of buccal absorption: Buccal drug absorption occurs by passive diffusion of the nonionized species, a process governed primarily by a concentration gradient, through the intercellular spaces of the epithelium. The passive transport of non-ionic species across the lipid membrane of the buccal cavity is the primary transport mechanism. The buccal mucosa has been said to be a lipoidal barrier to the passage of drugs, as is the case with many other mucosal membrane and the more lipophilic the drug molecule, the more readily it is absorbed. The dynamics of buccal absorption of drugs could be adequately described by first order rate process. Several potential barriers to buccal drug absorption have been identified. Dearden and Tomlison (1971) pointed out that salivary secretion alters the buccal absorption kinetics from drug solution by changing the concentration of drug in the mouth. The linear relationship between salivary secretion and time is given as follows: where, =dm _ KC dt weve M-— Mass of drug in mouth at time t K — Proportionality constant C - Concentration of drug in mouth at time Vi- The volume of solution put into mouth cavity and Vt- Salivary secretion rate 1.10 Factors affecting buccal absorption: The oral cavity are a complex environment for drug delivery as there are many interdependent and independent factors which reduce the absorbable concentration at the site of absorption. 1. Membrane Factors: This involves degree of keratinization, surface area available for absorption, mucus layer of salivary pellicle, intercellular lipids of epithelium, basement membrane and lamina propria. In addition, the absorptive membrane thickness, blood supply/ lymph drainage, cell renewal and enzyme content will all contribute to reducing the rate and amount of drug entering the systemic circulation. 2. Environmental Factors:A.) Saliva: The thin film of saliva coats throughout the lining of buccal mucosa and is called salivary pellicle or film. The thickness of salivary film is 0.07 to 0.10 mm. The thickness, composition and movement of this film affect the rate of buccal absorption. B.) Salivary glands: The minor salivary glands are located in epithelial or deep epithelial region of buccal mucosa. They constantly secrete mucus on surface of buccal mucosa. Although, mucus helps to retain mucoadhesive dosage forms, it is potential barrier to drug penetration, C.) Movement of buccal tissues: Buccal region of oral cavity shows less active movements. ‘The mucoadhesive polymers are to be incorporated to keep dosage form at buccal region for long periods to withstand tissue movements during talking and if possible during eating food or swallowing. 1.11 Composition of buccal patches A. Active Pharmaceutical ingredient (API): The buccal film technology has the potential for delivery of variety of APIs. However since the size of the dosage form has limitation, high dose molecules are difficult to be incorporated in buccal film. Generally S%w/w to 30%w/w of active pharmaceutical ingredients can be incorporated in the buccal patches. B. Polymers (adhesive layer): Polymer hydration and swelling properties probably play the main role. The polymer hydration and consequently the mucus dehydration could cause an increase in mucous cohesive properties that promote mucoadhesion, Swelling should favor polymer chain s, So, depending on the type flexibility and interpenetration between polymer and mucin chi of formulation.polymers with different characteristics have to be considered. Examples: Hydroxy ethylcellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, carbopol and other mucoadhesive polymers. C. Diluents: Lactose DC is selected as diluent for its high aqueous solubility, its flavouring characteristics, and its physico-mechanical properties, which make it suitable for direct compression. Other example ; microcrystalline starch and starch.D. Sweetening agents: Sucralose, aspartame, mannitol, etc. E. Flavouring agents: Menthol, vanillin,clove oil, Peppermint oil, cinnamon oil, spearmint oil, oi! of nutmeg are examples of flavor oils while vanilla, cocoa, coffee, chocolate and ete. F. Backing layer: Ethyl cellulose, etc G. Penetration enhancer: Cyano acrylate, EDTA, Ctric acid etc H. Plasticizers: PEG-100, 400, propylene glycol, etc. 1.12 Method of preparation: Two methods used to prepare adhesive patches include, 1. Solvent casting: In this, all patch excipients including the drug co-dispersed in an organic solvent and coated onto a sheet of release liner. After solvent evaporation, a thin layer of the protective backing material is laminated onto the sheet of coated release liner to form a laminate that is die-cut to form patches of the desired size and geomctry.The solvent casting method is simple, but suffers from some disadvantages, including long processing time, high cost, and environmental concerns due to the solvents used. These drawbacks can be overcome by the hot-melt extrusion method.ee Cee eo ELBE er LOR mn tants ee td dissolved in suitable solvent to form a clear viscous solution | TUR Cena } Resalting solution is cast as a film and allowed Cort Bones on) Fig no 2 : Pictorial diagram of Solvent casting method 2.Direet milling: In this, patches are manufactured without the use of solvents (solvent-free). Drug and excipients are mechanically mixed by direct milling or by kneading, usually without the presence of any liquids. After the mixing process, the resultant material is rolled on a release liner until the desired thickness is achieved. An impermeable backing membrane may also be applied to control the direction of drug release, prevent drug loss, and minimize deformation and disintegration of the device during application period. While there are only minor or even no differences in Patch performance between patches fabricated with the two processes, the solvent- free process is preferred because there is no possibility of residual solvents and no. associated solvent-related health issues.PE LUM vce eC Gle Mn at aree milling Blended mixture is rolled using rollers Backing material is laminated Film is collected Figno 3: Pictorial diagram of Direct ‘milling method 1.13 List of drug delivered via buccal route: In an effort to determine the feasibility of buccal route as a novel route of drug delivery, several drugs have been studied. The variation in class of compounds illustrates that the pharmaceutical industries have an alternative and novel routes of administration for existing drugs. > Active Ingredients: > Acitretin ® Acyclovir > Arecoline> Buprenorpine > Carbamazepine > Chitosan » Chlorpheniramine maleate » Metronidazole > Morphine sulphate > Nicotine > Nifedipine > Omeprazole > Oxytocin > Piroxicam > Exgotamine tartrate (etc). 1.14 Bloadhesive polymers Bioadhesive polymers are classified into two main categories. 1. Hydrophilic polymers that are water soluble 2. Water insoluble polymers that are swellable networks joined by cross-linking agents. In the large classes of hydrophilic polymers” those containing carboxylic group exhibit the best mucoadhesive properties. Poly vinyl pyrrolidine (PVP), methyl cellulose (MC), sodium carboxy methyl cellulose (SCMC), hydroxyl propyl cellulose (HPC) and other cellulose derivatives, Hydrogels are the class of polymeric biomaterial that exhibit the basic characteristics of an hydrogels to swell by absorbing water interacting by means of adhesion with the mucus that covers epithelia” i.e. * Anionic group — Carbopol, Polyaerylates and their cross linked modifications. * Cationic group - Chitosan and its derivatives = Neutral group -- Eudragit-NE30D ete1.15 Important Factors of Buccoadhesion High molecular weight (up to 000,000), High viscosity, Long chain polymers, Optimum concentration of polymeric adhesive, Flexibility of polymer chain, Spatial confirmation, Optimum cross-linked density of polymer, charge and degree of ionization of polymer? (anion > action > unionized), Optimum medium pH, Optimum hydration of the polymer, High applied strength and duration of its application and high initial contact time are some basic properties which a polymer must have to show a good mucoadhesive profile. Besides the above factors, some physiological factors, like mucin turnover and disease status also affect the Buccoadhesion. The mucin turnover is expected to limit the residence time of the buccoadhesives on the buccal mucosa. No matter, how high the buccoadhesive strength, buccoadhesives are detached from the surface due to mucin turnover. The physiochemical properties of the mucus are known to change during disease conditions such as cold, bacterial and fungal 8infections and inflammatory conditions, there by changing the degree of buccoadhesion Table 1, Related research on mucoadhesive polymers and delivery systems | Bioadhesive Polymer(s) Investigation Objectives Studied | HPC and CP Preferred mucoadhesive strength on CP, HPC, and HPC-CP combination HPC and CP Measured Bioadhesive property using mouse peritoneal membrane CP, HPC, PVP, CMC Studied inter polymer complexation and its effects on bioadhesive | strength | CP and HPMC Formulation and evaluation of buccoadhesive controlled release delivery systems HPC, HEC, PVP, and PVA Tested mucosal adhesion on patches with two-ply laminates with an impermeable backing layer and hydrocolloid polymer layer | HPC and CP Used HPC-CP powder mixture as peripheral base for strong adhesion and HPC-CP freeze dried mixture as core baseCP, PIP, and PIB | Xanthum gum and Locust bean gum | Chitosan, HPC, CMC, Pectin, Xantham gum, and Polycarbophil Hydroxyethylcellulose Polycarbophil Poly(acrylic acid) and | Poly(methacrylic acid) | Number of Polymers including HPC, HPMC, cP, CMC. Poly(acrylic a amide) co-acryl Used a two roll milling method to prepare a new bioadhesive patch formulation Hydrogel formation by combination of natural gums Evaluate mucoadhesive properties by routinely measuring the detachment force form pig intestinal mucosa Design and synthesis of a bilayer patch (polytef-disk) for thyroid gland diagnosis Design of a unidirectional buccal patch for oral mucosal delivery of peptide drugs Synthesized and evaluated cross linked polymers differing in charge densities and hydrophobicity Measurement of bioadhesive potential and to derive meaningful information on the structural requirement for bioadhesion Adhesion strength to the gastric mucus layer as a function of cross linking agent, degree of swelling, and carboxyl group density 1.16 Ablreviations:cP = Carbopol 934P, HPC = Hydroxy propyl cellulose, PVP = Poly(vinyl pyrrolidone), CMC = Sodium carboxymethyl cellulose, HPMC = Hydroxy propyl methyl cellulose, HEC = Hydroxy ethyl cellulose, PVA = Poly(vinyl alcohol), PIB = Poly(isobutylene), PIP = Poly(isoprene).2. LITERATURE REVIEW Shalini Mishra, G. Kumar, P. Kothlyal et al., Buccal drug delivery leads direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Buccal route is an attractive route of administration for systemic drug delivery, Buccal bioadhesive films, releasing topical drugs in the oral cavity at a slow and predetermined rate, provide distinct advantages over traditional dosage forms for treatment of many diseases. This article aims to review the recent developments in the buccal adhesive drug delivery systems to provide basic principles to the young scientists, which will be useful to circumvent the difficulties associated with the formulation design. Farheen Fiza et. Al., Drugs that are administered via the buccal mucosa direetly enter the systemic circulation, thereby avoiding hepatic first-pass metabolism. Therefore, this administration route is useful for improving the bioavailability of drugs that are subject to an extensive first-pass effect when delivered orally. For the oral mucosal route of drug administration, various types of dosage forms can be prepared. A sublingual tablet can afford rapid drug absorption and a prompt pharmacological effect; however, the duration of delivery is short owing to the inevitable loss of a large proportion of the administered dose due to swallowing. To avoid such losses, a patch can be formulated that is located on the buccal mucosa of the oral cavity. However, this approach is limited by the thicker dimensions of the buccal membrane compared to the others that line the oral cavity, and constraints impelled by the delivery system itself (the amount of drug reaching the systemic circulation is limited by the area of the mucosa that the patch covers, which, for patient comfort reasons, is relatively small). Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Sanket Sharma, R. Yogananda, Buccal administration of drug provides a convenient route of administration for both systemic and local drug actions. The preferred site for retentive oral transmucosal delivery systems and for sustained and controlled release delivery device is the buccal mucosa. Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of such drugs as potential therapeutic DEPARTMENT OF PHARMACEUTICS 15agents is their extensive pre-systemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Direct access to the systemic circulation through the internal jugular vein bypasses drug from the hepatic first pass metabolism leading to high bioavailability. The objective of this article is to review the developments in buccal adhesive drug delivery system as patches. Harsh et al., Esomeprazole is a class of drug called proton pump inhibitors used in treatment of gastro esophagus reflux disease. Buccoadhesive buccal delivery systems for esomeprazole in the form of unidirectional buccal patches were developed and characterized for improving bioavailability. The patches were formulated by solvent casting method using different bioadhesive polymers like HPMC 50cps and Eudragit RL-100 by using plasticizers glycerol and penetration enhancer tween-80, The physicochemical compatibility of the drug and the polymers was studied by FT-IR spectroscopy. The results suggested no physicochemical incompatibility between the drug and the polymers. Unidirectional release was achieved by preparing composite patches with backing membrane. The patches were characterized on the basis of their physical characteristics like weight uniformity, thickness, swelling studies, folding endurance, surface pH, bioadhesive performance, in vitro drug release and ex vivo drug diffusion. By evaluation of formulated patches we can find best formulation on basis of bioadhesive studies, in vitro drug release, ex vivo drug diffusion and folding endurance. Stability study of best formulations was carried out at different temperature as per ICH guidelines. Balakrishna et al., The present study deals with the formulation and evaluation of fast dissolving buccal films for effective treatment option in the gastroesophageal reflux disease. Methods: Esomeprazole fast dissolving buccal films are a convenient formulation of which can be taken with or without water. In the present investigation, polyvinyl alcohol and polyvinylpyrrolidone were used as film-forming agents and polyethylene glycol 400 is taken as plasticizer. Solvent evaporation method was used for the preparation of fast dissolving buccal films. Results: The films were prepared and evaluated for film thickness, folding endurance, dispersion test, drug content, and dissolution. The in vitro dissolution studies were carried out using simulated salivary fluid (pH 6.8 phosphate buffer). Conclusion: Among all the formulations, Formulation E7 was released up to 99.6% of the drug from the film within $ min of time which exhibits faster absorption and also shows desirable characteristics of the film, The drug-excipient interaction studies WERE carried out by Fourier-transform infrared a DEPARTMENT OF PHARMACEUTICS 16studies, differential scanning calorimetry analysis-X-diffraction studies, and scanning electron microscopic studies and the results revealed that there were no major interactions between the drugs and excipients used for the preparation of films. N-Vidyasagar et. al this review article is to describe the buccal drug delivery system of different dosage forms such as patches (films) and general considerations in formulation, types of buccal drug delivery dosage forms and describing different categories of drugs and their applications. Kinesh V. Patel et. al, This article reviews current status of various buccal bioadhesive dosage forms such as tablets, patches, hydrogels and chewing gums and describes the strategies to improve permeation of drugs through the Buccal mucosa. Recent innovations in Iso the dosage form development and in vivo and in vitro mucoadhesion testing methods ha: been focused. Lastly, different dissolution testing methods for buccoadhesive dosage forms developed by different researchers have also been discussed. Navneeth varma et al, Mucoadhesive Buccal patches of metoprolol Succinate were prepared by solvent casting method using chitosan, polyvinyl alcohol (PVA) and hydroxyethyl cellulose (HEC). Mucoadhesive properties and swelling index were determined for both plain and drug loaded patches. The results showed a remarkable increased in radial swelling after addition of drug to the plain patches. A decrease in the residence time was observed for PVA and Chitosan patches. A considerable decrease in release was observed for chitosan patches after the addition of water soluble excipient polyvinyl pyrrolidone (PVP). The in-vivo studies carried out on rabbits and evaluate % inhibition of Isoprenaline induced tachycardia. Ageing was done on the patches and the results showed there was no influence on the chemical stability of metoprolol, as reflected from the drug content result. Physical characteristics of the studied patches showed an increase in the residence time with storage accompanied with a decrease in drug release. Patel, Rajesh Singh; Poddar, S. S. et. al, present study was concerned with the preparation and evaluation of mucoadhesive buccal patches for the controlled systemic delivery of Salbutamol sulphate to avoid first pass hepatic metabolism. The developed patches were evaluated for the physicochemical, mechanical and drug release characteristics. The patches showed desired mechanical and physicochemical properties to withstand environment of oral cavity. The in-vitro DEPARTMENT OF PHARMACEUTICS 17release study showed that patches could deliver drug to the oral mucosa for a period of 7 h. the patches exhibited adequate stability when tested under accelerated conditions. Sw DEPARTMENT OF PHARMACEUTICS 183. AIM & OBJECTIVE OF STUDY The purpose of this study was to develop formulations and systematically evaluate in-vitro diffusion studies of buccal patches of Esomeprazole using different polymer and chose the polymer to develop the release of drug in immediate and sustained manner. The buccal route has a relatively robust mucosa, has the advantage of allowing excellent accessibility, and reasonable patient compliance. Within the oral mucosal cavity, the buccal region offers attractive route of administration for local or systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. Recently interest has been focused on the delivery of drug to or via mucous membrane by the use of mucoadhesive material, several mucoadhesive formulations are available under development and drug delivery via buccal mucosa is gaining importance of a novel route of drug administration. —_—_—————_—_—_——__ DEPARTMENT OF PHARMACEUTICS 20‘Type the document title PLAN OF WORK I. Literature survey Il. Preformulation studies © Preformulation study of Esomeprazole © Organoleptic Properties © Melting point of drug © Determination of solubility o Drug Excipient Compatibility studies III Preparation of Buccal patch by using various concentrations of Polymers TV Evaluations of Buccal pateh © Uniformity of weight of the patches Thickness uniformity of the patch © Swelling studies of the patches © Surface Ph © Drug Content Uniformity of Patches * Measurement of Mucoadhesive strength Measurement of Mucoadhesive Time © Folding endurance © In-Vitro Release Studies © Stability sudies V_ Result and discussion VI Conclusion Leone EET Department of Pharmaceutics Page 21[Type the document title 5. DRUG PROFILE Name: Esomeprazole Description: Esomeprazole is a 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2- yl)methyl|sulfinyl} -1 H-benzimidazole that has S configuration at the sulfur atom. An inhibitor of gastric acid secretion, it is used (generally as its sodium or magnesium salt) for the treatment of gastro-ocsophageal reflux disease, dyspepsia, peptic ulcer disease, and Zollinger-Ellison syndrome. It has a role as a histamine antagonist, an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor, an anti-ulcer drug and an EC 1.4.3.4 (monoamine oxidase) inhibitor. It is a conjugate acid of an esomeprazole(I-). It isan enantiomer of a (R}-omeprazole. Structure: Fig-: Molecular structure of Esomeprazole IUPAC Name: S)-(-)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin- 2-yl)methylsulfiny!]-3H-benzoimidazole Chemical Formula: C)7HisN303S Molecular weight: 345.42 g/mol i ee DEPARTMENT OF PHARMACEUTICS 24Type the document title CLINICAL PHARMACOLOGY: Mechanism of Action: Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump 2”, expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCI (gastric acid). Omeprazole is a member of a class of antisecretory compounds, the substituted henzimidazoles, that stop gastric acid secretion by selective inhibition of the H+/K+ ATPase enzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the H+/K+ ATPase pump, inhibiting gastric acid secretion for up to 36 hours. This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulus Pharmacodynamics: Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of crosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H’/K* ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid sectetion irrespective of the stimulus. Pharmacokinetics Absorption: 50-90 % Protein binding: Metabolism: Hepatic Route of elimination: Renal, biliary DEPARTMENT OF PHARMACEUTICS 25[Type the document title] Half life: 1-1.5 hrs Uses: Esomeprazole reduces the amount of acid your stomach makes. It's widely used to: treat indigestion, heartburn and acid reflux, and gastro-oesophageal reflux disease (GORD) - a condition which means you keep getting acid reflux. prevent stomach ulcers. DEPARTMENT OF PHARMACEUTICS 26Type the document title 6. EXCIPIENT PROFILE Hydro PMC) Synonyms: Methocel, Metolose, Pharmacoat, Benecel MHPC, E464 etc. Chemical name: Cellulose 2- hydroxyl propyl methyl ether H2OR rR Q re R SS n OR CH2OR Structural formula: Where R is H, CH3 or [CH3CH (OH) CH2] Fig-: Structure of HPMC Molecular weight: 10,000 — 15, 00,000 g/mol. Functional category: Bioadhesive material, coating agent, controlled-release agent. dispersing agent, dissolution enhancer, emulsifying agent, emulsion stabilizer, extended-release agent, film- granulation aid, modified-release agent, mucoadhesive, forming agent, foaming agent, gent, suspending agent, sustained release-modifying agent, solubilizing agent, stabilizing a release agent, tablet binder, thickening agent, viscosity-increasing agent. Description: Odourless and tasteless white or creamy white fibrous or granular powder. Solubility: Soluble in cold water, tically insoluble in forming a viscous colloidal solution: prac hot water, chloroform, ethanol (95%), and ether, but soluble in mixtures of ethanol and ane, mixtures of methanol and dichloromethane, and mixtures of water and dichlorometh: rades of HPMC are soluble in aqueous acetone solutions, mixtures of aleohol. Certain g -s are swellable in dichloromethane and propan-2-ol, and other organic solvents. Some grade ethanol. Melting point: Browns at 190°C-200°C; chars at 225°C-230°C. DEPARTMENT OF PHARMACEUTICSType the document title] Stability: HPMC powder is a stable material, although it is hygroscopic after drying. Solutions are stable at pH 3-11, Aqueous solutions are comparatively enzyme-resistant, providing good viscosity stability during long-term storage. However, aqueous solutions are liable to microbial spoilage and should be preserved with an antimicrobial preservative. Storage: Stored in a well-closed container, in a cool, dry place. Table-: Typical viscosity values for 2% (w/v) aqueous solutions of Methocel. Viscosities measured at 20°C. Methocel product Methocel K100 Premium LVEP Methocel K4M Premium USP 28 designation | Nominal viscosity (mPa s) Methocel KISM Premium Methocel K100M Premium Mcethocel E4M Premium, Methocel F50 Premium Mcthocel E10M Premium CR. 2906 Methocel E3 Premium LV Methocel ES Premium LV 2906 5 ae Se 0 0,000, 0000 Metolose 90SH 2906 50, 400, 1500, 4000 2208 100, 400, 4000, 15000 Applications: ——_—_—_—_—_—_—_—_—_—_—_—_—_—_—_—_—_—_—_———— DEPARTMENT OF PHARMACEUTICS 23[Type the document title’ ¥ In oral products, HPMC is primarily used as a tablet binder, in film-coating, and as a matrix for use in extended release tablet formulations. Concentrations between 2% and 5% w/w may be used as a binder in cither wet- or dry-granulation processes. High viscosity grades may be used to retard the release of drugs from a matrix at levels of 10-80% w/w in tablets and capsules. Hypromellose is also used in liquid oral dosage forms as a suspending and/or thickening agent at concentrations ranging from 0.25-5.0%. Y Depending upon the viscosity grade, concentrations of 2-20% w/w are used for film- forming solutions to film-coat tablets. Lower viscosity grades are used in aqueous film-coating solutions, while higher-viscosity grades are used with organic solvents Examples of film coating materials that are commercially available include AnyCoat C, Spectracel, Pharmacoat, and the Methocel E Premium LV series Y Hypromellose is also used as a suspending and thickening agent in topical formulations. Y Hypromellose at concentrations between 0.45-1.0% w/w may be added as a thickening agent to vehicles for eye drops and artificial tear solutions. It is also used commercially in liquid nasal formulations at a concentration of 0.1%. Y Hypromellose is used as an emulsifier, suspending agent, and stabilizing agent in topical gels and ointments. udragit : Eudragit RL100 is ammonio methacrylate copolymers consisting of fully polymerized copolymers of acrylic acid esters with 10% of functional quaternary ammonium groups Structural formula: Fig : Structure of Eudragit RL100 Nonproprietary Names: BP, PhEur, and USP-NF: ammonio methacrylate copolymer Synonym: Polymeric methacrylate oooeo_:::: DEPARTMENT OF PHARMACEUTICS. 24[Type the document title Chemical name: Poly (ethyl acrylate, methy] methaacrylate, trimethylammonioethyl metha- acrylate chloride) 1:2:0.2 CAS number: 33434-24-1 ‘Types: Eudragit RLPO, Eudragit RL12.5, Eudragit RL30D Description: Creamy-white granules Molecular weight: Approx. 32,000 g/mol Solubility: Soluble in Acetone and Alcohols including ethanol (95%), methanol and propane- 2-ol, dichloromethane, ethy! acetate. Eudragits RL100 is insoluble in petroleum ether and water. Density: 0.816 to 0.836 gmv/cm? Viscosity: <15 mPa Stability: Dry powder polymer forms are stable at temperatures less than 30°C. Above this temperature, powders tend to form clumps, although this does not affect the quality of the substance and the clumps can be readily broken up. Dry powders are stable for at least 3 years if stored in a tightly closed container at less than 30°C. Storage: Stored ina tightly closed container at less than 30°c. Applications: Film-forming agent; tablet binder; tablet diluents In the preparation of sustained release dosage forms. Methanol Synonyms — :Alcohol Emperical formula :C H 3 OH Structure: DEPARTMENT OF PHARMACEUTICS 25[Type the document title} Fig-: Molecular structure of Methanol ‘Molecular weight: 32 g/mol Applications: methanol is highly toxie and unfit for consumption. At room temperature, it is a polar liquid, and is used as an antifreeze, solvent, fuel, and as a denaturant for ethanol, It is also used for producing biodiesel via transesterification reaction, P col Non proprietary Names: > BP: Macrogols > JP: Macrogol 400 > PhEur: Macrogols > USP-NF: Polyethylene Glycol Synonyms: Carbowax; Carbowax Sentry; Lipoxol; Lutrol E; macrogola; PEG: Pluriol E: polyoxyethylene glycol. Chemical Name and CAS Registry Number: a-Hydro-w-hydroxypoly (oxy-1.2-ethanediyl) [25322-68-3] Structural Formula: 8 my — Re Sif H 4 Fig-+: Molecular structure of Methanol Solubility: All grades of polyethylene glycol are soluble in water and miscible in all Proportions with other polyethylene glycols (after melting, if necessary). Aqueous solutions of higher molecular weight grades may form gels. Liquid polyethylene glycols are soluble in acetone, alcohols, benzene, glycerine, and glycols. Solid polyethylene glycols are soluble in acetone, dichloromethane, ethanol (95%), and methanol; they are slightly soluble in aliphatic hydrocarbons and ether, but insoluble in fats, fixed oils, and mineral oil. DEPARTMENT OF PHARMACEUTICS 26Type the document title] Functional Category: Ointment base; plasticizer; solvent; suppository base; tablet and capsule lubricant. Applications in Pharmaceutical Formulation or Technology Polyethylene glycols (PEGs) are widely used in a variety of pharmaceutical formulations, including parenteral, topical, ophthalmic, oral, and rectal preparations. Polyethylene glycol has been used experimentally in biodegradable polymeric matrices used in controlled-release systems. Dimethylsulfoxide Synonyms : Methylsulfinylmethane, Methyl sulfoxide Emperical formula :C H 3 OH Structure: 9 S H3C~~ “CHg Fig: Molecular structure of DMSO Molecular weight: 78 g/mol Molecular formula: C2HoOS Applications: It is used as permeation enhancer in patch preparations DEPARTMENT OF PHARMACEUTICS 27[Type the document title] 7, MATERIALS AND EQUIPMENTS Table-: List of Materials used S.NO MATERIALS SUPPLIER 1 Esomeprazole Hetero labs, HYD Syn pharma research labs, HYD 2 HPMC k 100M. 3 Syn pharma research labs, HYD Eudragit Syn pharma research labs, HYD 4 Methanol (ml) Syn pharma research labs, HYD 5 Poly ethylene glycol Syn pharma research labs, HYD 6 DMSO. DEPARTMENT OF PHARMACEUTICS 29Type the document title] Table-: List of equipments used S8.NO EQUIPMENT NAME SOURCE 1 Digital weighing machine Shimadzu aty 244 UV-Visible double beam Lab india UV visible double 2 spectrophotometer beam spectrophotometer 3 Franz diffusion cell AR chemicals, HYD 4 Magnetic stirrer Erweka 5 Bath sonicator Wensar DEPARTMENT OF PHARMACEUTICS. 30[Type the document title 8. METHODOLOGY PREFORMULATION STUDIES Methods of API characterization Physical properties The color, odour, taste of the drug were recorded. Solubility studies Solubility study of Esomeprazole was performed in Water, methanol, ethanol, and pH 6.8 phosphate buffer. Determination of melting point: M. P of Esomeprazole was estimated by capillary method. Preparation of phosphate buffer pH 6.8: 28.85 gms of di- sodium hydrogen orthophosphate and 11.45gm of potassium dihydrogen phospghate was weighed to it sufficient water was added to get 1000 ml and the pH was altered to 6.8 with Ortho phosphoric acid. Standard curves of Esomeprazole : Standard graph of Esomeprazole in phosphate buffer 6.8: Standard stock solution of Esomeprazole (Img/ml) was prepared by dissolving 100mg of Esomeprazole in 100ml of methanol. Diluting the standard stock solution with phosphate buffer 6.8, solution of 100 jig/ml concentration was prepared. From this solution serial dilutions were made with phosphate buffer 6.8 to get 10, 20, 30, 40, 50 ug/ml concentrations. These solutions were checked for the absorbance using UV- Visible spectrophotometer at 4 max against phosphate buffer 6.8 as blank and standard graph was plotted by taking concentration on X- axis and absorbance on Y- axis. Compatibility studies of drug and polymers: DEPARTMENT OF PHARMACEUTICS 42[Type the document title In the formulation of Esomeprazole patch formation , API and Excipient may interact as they are in close communication with each other, which could lead to the instability of drug. FT- IR spectroscopy was employed to ascertain the compatibility between Esomeprazole and the selected polymers. The pure drug and drug with excipients were scanned separately. Formulation design: Table-: Formulation Design of Esomeprazole buccal Patches Ingredients (mg) F.Code| prug HPMC No Eudragit PEG DMSO (ng) | k100M 1 | FL 100 100 - Iml 0.1m! 2 F2 100 200 * ml 0.1ml = F3 100 “ 100 Iml 0.1ml 4 | Fa 100 - 200 Iml o.1ml Preparation method: Solvent casting method Esomeprazole buccal patches were formulated by the solvent casting evaporation technique. ‘The drug Esomeprazole was diffuse in methanol. Polymers HPMC K100M, cudragit were taken in a boiling tube, to this add Esomeprazole drug which was previously dissolved in suitable solvent. Sufficient care was taken to prevent the creation of lumps. PEG was taken as a plasticizer and Dimethylsulfoxide as permeation enhancer and added to the mixture and mixed well. It was set aside for 2 hours to exclude any entrapped air and was then transferred into a previously cleaned petri plate (40em”), drying of patches was carried out in vacuum ‘oven at room temperature. Dried patches were packed in aluminium foil and stored in a desiccator for further evaluation. Characterization of Buccal formulation jical evaluation Physico- chet DEPARTMENT OF PHARMACEUTICS 43[Type the document title] Physical appearance: All the formulated Esomeprazole films were observed for color, clarity, flexibility, and smoothness. Folding endurance: Buccal patches folding endurance was estimated by frequently double over at the same place till it broke. The number of times the film could be folded at the same place without breaking is the folding endurance. This was restate on all the films for three times and the mean values plus standard deviation was calculated. Thickness of the film: The thickness of cach film was measured by using screw gauze. Buccal patches thickness ‘was estimated at various sites on each patch and the average thickness of the Buccal patch was capture as the thickness of the patch. Weight uniformity: ‘The formulated Buccal patches are to be dried at 60°C for 6 hours before trial. A identify the area of 4.52 cm’ of film is to be cut in different parts of the patch and weigh in digital balance. The average weight and standard deviation values are to be calculated from the individual weights. Drug content : The formulated Buccal patch were assayed for drug content in each case. Three patches from each formulation were assayed for content of drug. Each formulation was casted in triplicate and one patch from each was taken and assayed for content of drug. The Buccal films (4.52 cm?) were added to conical flask containing 100 ml of phosphate buffer pH 7.4 contain 0.5% SLS. This was then stirred with magnetic bead at 400 rpm for 2 hrs. The contents were filtered and the filtrate was analyzed spectrophotometrically. Similarly a blank was prepared from Buccal films without drug. Molsture absorption studies: The buccal patches were weighed exactly and placed in a desiccators containing aluminium chloride to maintain 79.50% RH. After 3 days, the films were taken out and weighed. The percentage of moisture uptake was calculated using the following formula. DEPARTMENT OF PHARMACEUTICS 44[Type the document title’ Final weight — Initial weight Initial weight be Perentage moisture uptake = Moisture loss studies: Three patches were weighed separately and kept in a desiccator contains calcium chloride at 37°C for 24 hours. Then the last weight was noted when there was no further change in the weight of the patch. The percentage of moisture loss was calculated using the following formula. Initial weight — Final weight Final weight * 100 Percentage moisture loss = In Vitro release study: The release rate of the drug was determined by using Franz diffusion cell apparatus temperature maintained at 37 + 0.5 °C and stirred at a rate of 200 rpm. Sink conditions was maintained all over the study. The vessel containing 10ml of phosphate buffer pH 6.8 phosphate buffer solution. Aliquots of Iml of samples were withdrawn at various time meanwhile and then analyzed using a UV Spectrophotometer. % release rate of drug was determined using the following formula, D Perentage drug release = me x 100 Where, Dt = Total amount of the drug in the film Da = The amount of drug released Conditions: Medium: Phosphate buffer pH 7.4 phosphate buffer RPM: 200 Temperature: 37 + 0.5°C Time intervals: 1,2, 3,4, 5, 6, 7, 8 hours. DEPARTMENT OF PHARMACEUTICS 45[Type the document title] Fig-: Franz diffusion cell Stability studies: Optimized medicated buccal films were subjected to short term stability testing. The Buccal films were sealed in aluminium foils and kept in a humidity chamber maintained at 40 + 2 °C and 75 4 5% RH for 3 months as per ICH guidelines. DEPARTMENT OF PHARMACEUTICS 46[Type the document title] 9. RESULTS AND DISCUSSION Active pharmaceutical ingredient characterization Physical properties The color odour, taste of the drug were recorded using descriptive terminology. Solubility studies Solubility study of Esomeprazole was performed in dimethyl sulphoxide, methanol, ethanol, chloroform and insoluble in water. Melting point determination: The results of partition coefficient and melting point are tabulated in table. Table-: Determination of Melting point Melting point (°C) 162°C Determination of ). max using UV- Visible spectrophotometer: Esomeprazole exhibits absorption maxima at 289 nm in phosphate buffer 6.8 Determination of absorption maxima (ma) for Esomeprazole A 1Omcg/ml standard solution of Esomeprazole was scanned on a double beam spectrophotometer against respective media blanks. An absorption maximum (Ama) of 289 thm was obtained for all solutions and was selected to prepare standard curve. Leer err DEPARTMENT OF PHARMACEUTICS, 39[Type the document title] Table-: Calibration curve of Esomeprazole S. no ‘Concentration (ug/ml) Absorbance 1 0 0 2 10 0.132 3 20 0.234 4 30 0.327 5 40 0.435 6 50 0.543 Calibration curve of Esomeprazole 06 y= 0.0106x + 0.013 os RE= 0.9978 goa fos 3 2 —® Absorbance O27 —Linear (Absorbance) O1 1 0 0 20 40 60 Concentration pg/ml Fig-: Calibration curve of Esomeprazole Compatibility studies of drug and polymers: All these peaks have appeared in formulation and physical mixture, indicating no chemical interaction between Esomeprazole and polymer. It also confirmed that the stability of drug during microencapsulation process. DEPARTMENT OF PHARMACEUTICS: 40Type the document title 8 <== sae \ rN a \ [ Me Fg | Mt) 4) i ty \ fe | z | | ‘ 3 | ' i ! ee t as ¥ E ii fea gg a 3500 3000 2500 00 1600 1000 Waverumber cme Fig-: FTIR Studies of Esomeprazole Table-: Characteristic Peaks for Esomeprazole S.No.] Characteristic Peaks | Frequency Frequency (cm-I) range (cm-I) 1 OH stretching 3500-3000 3411.80 a OH Bending 1000-1500 1222.35 3 C-H stretching 3000-2500 2926.39 4 C=0 stretching 2000-1500 1706.99 DEPARTMENT OF PHARMACEUTICS, AL[Type the document title e 3 \ 20 3600 3000 2500 2000 1500 1000 \Wervenumber om-1 Fig-: FTIR Studies of Physical mixture of drug and excipients Table-: Characteristic Peaks for Physical mixture of drug and excipients S.No. | Characteristic Peaks | Frequency Frequency (em-1) range (cm-1) 1 OH stretching 3000-2500 2916.84 2 OH Bending 1100-1070 1071.96 3 C=O stretching 2000-1500 1575.23 Physical appearance and surface texture of buccal patches: These parameters were checked simply with visual inspection of patches and by feel or touch The observation reveals that the patches are having smooth surface and they are elegant in appearance. Welght uniformity of buccal patches: The weight of the patches was determined using digital balance and the average weight of all patches DEPARTMENT OF PHARMACEUTICS 42Type the document title Thickness of buccal patches: The thickness of the patches was measured using screw gauge and the average thickness of all patches. Folding endurance of buceal patches: The folding endurance gives the idea of flexible nature of patches. The folding endurance was measured manually, patches were folded repeatedly till it broke, and it was considered as the end point. The folding endurance was found optimum and the patches exhibited good Physical and mechanical properties and the average folding endurance of all patches. Drug content uniformity of buccal patches: Esomeprazole buccal patches prepared with various polymers were subjected to the valuation for uniform dispersion of drug throughout the patch. In each case three patches were used and the average drug content was calculated, % moisture loss: The moisture content in the buccal patches ranged from 8.75 to 8.96%. The moisture content in the formulations was found to be increased by increase in the concentration of polymers. Yemolsture absorption: The moisture absorption in the buccal patches ranged from 7.14to 7.47 %. Swelling index: The swelling index in the buccal patches ranged from 14.50 to 15.47 %. DEPARTMENT OF PHARMACEUTICS. 43‘Type the document title] Table -: Physicochemical evaluation data of Esomeprazole Buccal Patches F. code Fi F2 | F3 F4 Thickness (mm) 032 | 027 | 030 | o28 47.89 Weight variation (mg) | 44.89 45.24 | 46.90 Drug content| 96.30 | 93.86 | 94.25 | 92.59 Uniformity 83 Folding endurance 80 79 82 % moisture loss TAT 7.56 TAL 7.82 Yemolsture absorption 8.14 837 | 819 | 8.20 Swelling index 15.10 14.86 | 14.50 | 15.47 Drug release studies Table-: /n vitro release data of film Fi to Fs Time | Fi ri Bs Fa (hrs) o [0 0 0 0 ' 15.12 | 14.16 | 13.48 15.28 2 25.79 | 25.91 | 27.50 26.91 3 38.82 | 37.82 | 38.93 39.55 4 49.18 | 47.93 | 45.12 48.26 * 62.85 | 69.15 | 68.55 67.24 6 7745 | 7245 | 72.11 76.18 7 88.93 | 87.80 | 86.07 82.14 DEPARTMENT OF PHARMACEUTICS 44Type the document title 8 | 95.90 | 92.66 | 91.52 93.58 In vitro drug release 120 300 80 60 40 20 ° o 1 2 3 4 5 6 7 g 4 el eR ers ery Fig-: In vitro drug release of (F1- F4) formulation Stability studies: Optimized formulations F1 was selected for accelerated stability studies as per ICH Buidelines. The patches were observed for color, appearance and flexibility for a period of three months. The folding endurance, weight, drug content, % cumulative drug release of the formulation was found to be decreasing. This decrease may be attributed to the harsh environment (40°C) maintained during the studies, Table-: Stability studies of optimized formulations Mean % drug release Time | Physical S.NO |in | changes Esomeprazole days 25°C 160% 30°C/75% 40°C/75% 1. | 01 | Nochange | 95.90 95..90 95.90 K+ 90 | No Change 94.09 DEPARTMENT OF PHARMACEUTICS[Type the document title] 10, SUMMERY & CONCLUSION From the present research work that is development and evaluation of Esomeprazole buccal patches for buccal drug delivery. the following points can be concluded: The patches prepared were elegant in appearance and smooth surface The weights of patches were uniform. The thicknesses of patches were uniform. The patches were completely dried. The patches had good flexibility. The patches shows uniform swelling index. There was no drug-excipients interaction between the drug and excipients used in the formulation. The drug was distributed throughout the patch uniformly. More than 85 % of the drug was released from all the formulations at the end of 8 hrs. In short term stability studies indicate there were no significant changes in the drug content and in-vitro drug release for the period of three month. From the result and conclusion of the research work we can summarize that Esomeprazole can be delivered via buccal route, ee DEPARTMENT OF PHARMACEUTICS. 59[Type the document title] 11. REFERENCES Shoba Rani R Hiremath; Industrial Pharmacy, Orient Longman private limited, 2008; First edition, 73-77. . Sang-Chul Shin, Jin-Pil Bum, Jun-Shik Choi. Enhanced bioavailability by buccal administration of triamcinolone acctonide from the bioadhesive gels in rabbits, Int. J. Pharmaceutics., 2009; 209:37-43. . 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