International Journal of Research in Pharmacy and Pharmaceutical Sciences
www.pharmacyjournal.in
ISSN: 2455-698X
Received: 05-10-2023, Accepted: 23-10-2023, Published: 08-11-2023
Volume 8, Issue 4, 2023, Page No. 20-25
Formulation and evaluation of floating drug delivery system of fosinopril
Preethu M N, Nagendra R, Venkatesh, P.K.Kulkarni, K Hanumanthachar Joshi
Department of Pharmaceutics, Sarada Vilas College of Pharmacy, Karnataka, India
Abstract
The present research work is an attempt to develop and evaluate floating drug delivery system of Fosinopril in order to
improve drug bioavailability. A floating drug delivery system helps toimprove the buoyancy property of the drug over gastric
fluids so it maintains the longer duration of action this also helps in minimizing the dosing frequency. Floating tablets of
Fosinopril were prepared with solid dispersion by physical mixture by usingPEG4000.Tablets are prepared with the direct
compression method by using HPMC K4M, HPMC K15M and Carbopol as polymer. Fosinopril floating tablets were prepared
utilising both separate and combined polymers. Different ratios of the polymers HPMC, Carbopol 940, and guar gum were
utilised. Five formulations in total (AF1–AF5) were prepared. All the formulations were subjected for the flow properties—
bulk density, tap density, and angle of repose- the results were found to bewithin the acceptable range. The direct compression
method was used to prepare the flotation tablets of Fosinopril. The direct compression approach is quick, easy, and labor-
intensive. These formulations (AF1-AF5) were examined for a number of tests, including dissolving studies, homogeneity of
content, friability, and weight fluctuation. In vivo studies to evaluate the performance and application of floating systems, and
applications of these systems. Thesesystems are useful to several problems encountered during the development of
apharmaceutical dosage form. The formulations (AF1) made with HPMC and (AF2) made with Carbopol 940 both
demonstrated good floating times of 8 hours. With a floating time of 8 hours and a drug release of roughly 98.4% at the end of
24 hours, the formulation (AF1) containing hydroxypropyl methylcellulose was discovered to be the optimum formulation.
Keywords: Fosinopril, bioavailability, floating drug delivery, direct compression, HPMC
Introduction Under reasonably regulated circumstances, the pH of the
The most promising, secure, and efficient method of drug stomach causes drug disintegration and release from the
delivery is thought to be oral. Various factors, including the dose form held in the fluids. The dose form's retentive
gastric emptying process, the gastrointestinal transit time of properties are not important for the medications that [5].
the dose form, and the drug release from the oral cavity, ▪ Are insoluble in intestinal fluids
may affect the effectiveness of oral medication delivery, ▪ Act locally
dose type and location of drug absorption [1]. ▪ Exhibit site specific absorption
The majority of oral dosage forms have a number of
physiological constraints, including variable gastrointestinal Advantages of Gastoretentive drug delivery System
transit, which results in nonuni form drug release, partial The following benefits of gastroretentive medication
drug release, and shorter dosage form resident times in the delivery systems are just a few;
stomach [2]. This causes inadequate absorption of ▪ HBS can be used to any specific medication or set of
medications with absorption windows, particularly in the medications.
upper region of the small intestine, as the drug's remaining ▪ In contrast to medications, which are primarily
amount is not absorbed after it passes through the absorption absorbed via the stomach, HBS formulations are not
site. Wide inter- and intra-subject variability are seen as a just for medications. Due to the fact that studies have
result of numerous factors affecting the stomach emptying shown that these are just as effective as drugs that are
of dose forms in humans. Such significant variability may absorbed from the intestine, such as chlorpheniramine
cause non-uniform absorption as many medications are well maleate.
absorbed in the upper region of the gastrointestinal track, ▪ The HBS are beneficial for medications that are
making the bioavailability uncertain. As a result, a delivery absorbed via the stomach, such as ferrous salts, and for
system that can regulate and extend stomach emptying time medications intended for local action in the stomach,
as well as transport medications in higher concentrations to such as those used to treat peptic ulcer disease. eg;
the absorption site (i.e. the upper part of the small intestine) antacids.
would be useful [3]. ▪ It has been discovered that the site of the specific
Many FDDS have been developed recently that use a variety medications' site of absorption has no bearing on the
of technologies, each with unique benefits and drawbacks. effectiveness of the medications delivered using the
Examples include single and multiple unit sustained release principle of HBS.
hydrodynamically balanced systems (HBS), single and ▪ When a prolonged release floating dosage form tablet
multiple unit gas generating systems, hollow microspheres, or capsule is taken, the medication will dissolve in the
and raft forming systems [4]. stomach juices. Following stomach emptying, the
A drug's formulation known as FDDS uses hydrocolloids medicine that has been dissolved is ready for small
that form gels to stay buoyant in the stomach's contents. intestine absorption. Therefore, it is anticipated that a
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International Journal of Research in Pharmacy and Pharmaceutical Sciences www.pharmacyjournal.in
medication will be completely absorbed from the Loss on drying
floating dosage form if it stays in solution form even at 10gms of Fosinopril was heated to a temperature of 105ºC
the intestine's alkaline pH. in hot air oven until it remains constant weight. The formula
▪ It may be helpful to keep the medicine in a floating was
condition in the stomach to elicit a substantially better
reaction when there is vigorous intestinal movement
and a short transit period, as can occur in some types of
diarrhea.
Angle of repose
▪ Benefits of gastric retention include the administration
Angle of repose is defined as the maximum angle possible
of medications with limited small intestine absorption
between the surface of the pile of powder and the horizontal
windows.
plane. The angle of repose is designated by θ. It was
▪ Traditional extended-release development is difficult
determined by funnel method. The powder blend was passed
since many medications designated for once-daily
through funnel so that it forms a pile. The height(h) of the
delivery have been shown to have sub-optimal
pile and the radius of the pile (r) were measured and angle
absorption due to dependence on the transit time of the
of repose was calculated using following formula.
dosage form. As a result, a system made for extended
stomach retention will lengthen the window of time
θ = tan-1(h/r) Bulk
during which drugs can be absorbed in the small
intestine.
Density & Tapped density
Bulk density and tapped density were calculated by the
Disadvantages of Gastroretentive drug delivery System
formula.
▪ Gastric retention is not preferred in several
circumstances. It is undesirable for these medications to
release slowly in the stomach since aspirin and non-
steroidal anti- inflammatory drugs are known to cause
gastric lesions.
▪ As a result, medications that could aggravate the Hausner’s ratio
stomach lining or become unstable in the stomach's It was calculated as
acidic environment shouldn't be created in
gastroretentive systems.
▪ Additionally, a gastric retention system won't help other
medications that are similarly well absorbed throughout
the GI tract, including isosorbide dinitrate.
▪ Numerous elements, including stomach motility, pH, Compatibility Studies
and the presence of food, might affect gastric retention.
Since these variables are never constant, it is impossible FTIR Spectroscopy
to anticipate the buoyancy precisely or accurately. Infrared spectrum obtained for pure Fosinopril. In order to
▪ In supine subjects, gastric emptying of floating forms confirm that the drug and the excipients employed in the
may happen at random and become highly reliant on formulation development were chemically compatible, a
the diameter. As a result, administering floating forms physical combination of the drug and several polymers was
to patients right before bedtime is not advised. used. In order to create the IR spectrum that was used for
▪ Due to differences in the emptying process, there is a identification, 2-3 mg of sample were combined with
high degree of variability in gastric emptying time. potassium bromide and pelleted (dried at 40–50⁰C). A piece
▪ Unpredictable bioavailability. of the mixture was compacted into a clear pellet using a
hydraulic press and 10 tonnes of pressure. The FT-IR
Methodology spectrophotometer scanned the particle. FTIR spectrometer
Preformulation Studies of Fosinopril was used to scan the material from 4000-400cm-1.
Preformulation is the process of using biopharmaceutical
principles to modify a drug's physical qualities. It is a step in Standard Graph of Fosinopril
the R&D process. Fosinopril standard solution in acid buffer pH 1.2,
phosphate buffer pH 6.8 & pH 7.4 containing 5 to 50g was
Primary Characterisation of active ingredients and used to generate standard graphs of the medication. At
additives, Description of Fosinopril. 275nm, the absorbance was measured. The connection
5.0 mg of the sample was taken in Petri dish was spread between medication concentration and absorption was
carefully and recorded colour, odour and texture. linear.
Melting point Formulation of Floating Tablets of Fosinopril
Fosinopril's melting point was established using the
capillary method. Finely grinded Fosinopril powder was
placed in a glass capillary tube that had been previously
sealed on one end. The drug-filled capillary tube was then
placed inside the melting point apparatus, and the
temperature at which the drug began to melt was monitored
using a thermometer.
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International Journal of Research in Pharmacy and Pharmaceutical Sciences www.pharmacyjournal.in
In vitro Dissolution Studies
In vitro dissolution carried out using USP Dissolution
Testing apparatus (paddle) type. The dissolution test
performed using 900 ml of 0.1 N HCL maintaining normal
body temperature, 10 ml of the sample withdrawn at
predetermined interval for 12 hours and fresh volume
introduced and its absorbance is measured and cumulation
percentage drug release is measured.
Description of Active ingredients
Table 1
Sl.no Components Fosinopril
1 Colour White
2 Odor Odourless
3 Texture Powder
Identification test.
Identification was carried out as described in Table 5. The
observed results were presented in Table 10. Additives that
were used in the preformulation studies, for which
identification test were performed (IP 2006). Ugwoke et al.,
2005 states that before the development of formulation
excipients quality is must be identified.
Fig 1 Table 1: Identification test of Fosinopril
Sl. No Ingredients Observation Inference
Differential Scanning Calorimetry studies of Fosinopril.
To investigate the physical and chemical interactions A white
precipitate Carbopol may be
between the medicine and the applied excipients, 1 Carbopol
immediately confirmed.
differential scanning calorimetry (DSC) was used. On the forms.
DSC-60 equipment, DSC spectra of pure drugs and drug Hydroxy
composite mixtures were captured. The drug-excipient Hydroxy Propyl
Propyl No precipitate
2 Methyl Cellulose
mixture was scanned in a nitrogen-filled environment Methyl appears
may be confirmed.
between 50 and 400°C. All samples were prepared in Cellulose
aluminium pans with aluminium covers.
FTIR studies of Fosinopril.
Fig 2: FTIR Spectra of Fosinopril
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Fig 3: FTIR Spectra of Fosinopril + Carbopol 940
Fig 4: FTIR Spectra of Fosinopril + Guar gum
Fig 5: FTIR Spectra of Fosinopril + HPMC
In an effort to investigate the possible chemical interaction (a) Fosinopril; (b) Carbopol 940; (c) Guar gum;(d) HPMC.
of drug with polymer, that have been analyzed Fosinopril has shown a characteristic peak at 1778.43 cm -1,
which shows C=C, broad band at 3333.10 cm-1, shows a
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International Journal of Research in Pharmacy and Pharmaceutical Sciences www.pharmacyjournal.in
characteristic peak at 3128.64 cm-1, which is responsible for Table 3: Standard plot of Fosinopril
C-NH, a sharp peak at 1360.62 cm-1 due to the presence of Concentration Absorbance
C-N. 0 0
10 0.201
Table 2: Characteristics of final blend of Fosinopril floating 20 0.346
matrix tablets 30 0.501
Bulk Tapped 40 0.654
Hausner’s 50 0.799
Formulations Angle of density density
repose (θ) (g/ml) (g/ml) ratio
F1 21o.32’ 0.365 0.386 13.53
F2 220.15′ 0.345 0.412 13.79
F3 210.23′ 0.343 0.417 13.98
F4 230.36′ 0.351 0.387 13.45
F5 240.18′ 0.344 0.415 12.31
Differential Scanning Calorimetry studies of Fosinopril.
Thermograms for pure Fosinopril and mixed matrix floating
tablets comprising Fosinopril and other excipients were both
obtained. This depicts the melting endotherm for pure
powdered Fosinopril, which occurred at 327.30 °C. In
neither sample did the drug's melting point alter noticeably.
It proves the substance existed in its distinctive physical and Fig 8: Calibration curve of Fosinopril In-vitro Dissolution Study.
molecular form.
Each dissolution vessel of the dissolving paddle apparatus
contained 900ml of newly prepared dissolution medium, i.e. 0.1N
HCl, and was rotated at 75 rpm while being kept at a temperature
of 37+/-0.50C. Fosinopril pills were dissolved in a solution. Every
0, 1, 2, 4, 8, 12, 16, 20 and 24 hours, about 5 ml of the dissolution
liquid were pipetted out, and the volume was adjusted by
substituting 5 ml of 0.1N HCl. The aforementioned samples,
totaling 5ml (7 samples), were gathered in a volumetric flask and
diluted with 0.1N HCl to generate 10ml. Finally, a UV
spectrometer set to 275 nm was used to measure the solution's
absorbance.
Conclusion
Fosinopril floating tablets were prepared utilising both separate
and combined polymers. Different ratios of the polymers HPMC,
Fig 6: DSC thermogram of Fosinopril Carbopol 940, and guar gum were utilised. Five formulations in
total (AF1–AF5) were prepared. All the formulations were
subjected for the flow properties—bulk density, tap density, and
angle of repose- the results were found to be within the acceptable
range. The direct compression method was used to prepare the
flotation tablets of Fosinopril. The direct compression approach is
quick, easy, and labor-intensive. These formulations (AF1-AF5)
were examined for a number of tests, including dissolving studies,
homogeneity of content, friability, and weight fluctuation.
Acknowledgement
We sincerely acknowledge the Guide, Management, Principal,
HOD, Teaching and Nonteaching staff of Sarada Vilas College of
pharmacy, Mysuru for their endless support and suggestions
throughout the research work.
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