ABSTRA CT
The oral route is considered as the most promising route of drug
delivery. Several approaches have been or suspension systems and sachet
systems. Floating systems have low bulk density so that they can float on the
situation, there is nothing to float on. It shows absorption window in stomach
area, which makes it suitable attempted in the preparation of gastro-retentive
drug delivery systems. These include floating systems, swell able and
expandable systems, high density systems, bio adhesive systems, altered shape
systems, gel forming solution gastric juice in the stomach. The problem arises
when the stomach is completely emptied of gastric fluid. In such as candidate
for gastro retentive dosage forms. The aim and objective of the study is to
develop a floating tablet of Norfloxacin to minimize the frequency of dosing by
increasing dissolution and sustained release action up to 12 hrs by single unit
dosage. Floating tablet of Norfloxacin, consist of HPMC polymer and sodium
bicarbonate as gas generating agent, were formulated by direct compression
method. It was found that the prepared formulation have a floating lag time
4min 38 sec and constantly float on dissolution medium for more than 10 hrs.
(1) Background: Many drugs possess poor bioavailability, and many strategies
are available to overcome this issue. In this study, smartFilm technology, i.e., a
porous cellulose matrix (paper), in which the active compound can be loaded
onto in an amorphous state was utilised for oral administration to improve the
solubility and bioactivity of a poorly soluble BSC class IV antibiotic.
(2) Methods: Norfloxacin was used as the model drug and loaded into
commercially available paper. The resulting norfloxacin-loaded smartFilms
were transformed into smartFilm granules via wet granulation and the resulting
norfloxacin-loaded smartFilm granules were transformed into norfloxacin-
loaded tablets made from paper, i.e., smartFilm tablets. The crystalline state of
norfloxacin was investigated, as well as the pharmaceutical properties of the
granules and the tablets. The bioactivity of the smartFilm tablets was assessed in
vitro and ex vivo to determine the antibacterial activity of norfloxacin. The
results were compared to a physical mixture tablet that contained non-loaded
paper granules and equal amounts of norfloxacin as a crystalline powder.
(3) Results: Norfloxacin-loaded smartFilm granules and norfloxacin-loaded
smartFilm tablets contained norfloxacin in an amorphous state, which resulted
in an improved and faster release of norfloxacin when compared to the physical
mixture tablet. The bioactivity was up to three times higher when compared to
the physical mixture tablet. The ex vivo model was demonstrated to be a useful
tool that allows for a fast and cost-effective discrimination between “good” and
“bad” formulations. It provides realistic physiological conditions and can
therefore yield meaningful, additional biopharmaceutical information that
cannot be assessed in classical in vitro experiments.
(4) Conclusions: smartFilm tablets are a promising, universal, industrially
feasible and cost-effective formulation strategy for improved solubility and
enhanced bioactivity of poorly soluble drugs.
INTRODUCTION
Floating drug delivery systems (FDDS) or hydro dynamically
controlled systems are low-density systems that have sufficient buoyancy to
float over the gastric contents and remain buoyant in the stomach without
affecting the gastric emptying rate for a prolonged period of time. While the
system is floating on the gastric contents, the drug is released slowly at the
desired rate from the system. After release of drug, the residual system is
emptied from the stomach. This results in an increased Gastric retention time
and a better control of the fluctuations in plasma drug concentration. However,
besides a minimal gastric content needed to allow the proper achievement of the
buoyancy retention principle, a minimal level of floating force (F) is also
required to keep the dosage form reliably buoyant on the surface of the meal
many buoyant systems have been developed based on granules, powders,
capsules, tablets, laminated films and hollow microspheres.
Gastric emptying of dosage forms is an extremely variable
process and ability to prolong and control the emptying time is a valuable asset
for dosage forms, which reside in the stomach for a longer period of time than
conventional dosage forms. Several difficulties are faced in designing controlled
release systems for better absorption and enhanced bioavailability. One of such
difficulties is the inability to confine the dosage form in the desired area of the
gastrointestinal tract. Drug absorption from the gastrointestinal tract is a
complex procedure and is subject to many variables. It is widely acknowledged
that the extent of gastrointestinal tract drug absorption is related to contact time
with the small intestinal mucosa¹. Thus, small intestinal transit time is an
important parameter for drugs that are incompletely absorbed.
Gastroprotective systems can remain in the gastric region for several hours
and hence significantly prolong the gastric residence time of drugs. Prolonged
gastric retention improves bioavailability, reduces drug waste, and improves
solubility for drugs that are less soluble in a high pH environment. It has
applications also for local drug delivery to the stomach and proximal small
intestines. Gastro retention helps to provide better availability of new products
with new therapeutic possibilities and substantial benefits for patients.
The controlled gastric retention of solid dosage forms may be achieved by the
mechanisms of mucoadhesion, flotation, sedimentation, expansion , modified
shape systems, or by the simultaneous administration of pharmacological
agents that delay gastric emptying.
Based on sification of floating drug delivery systems (FDDS) has been
described in detail. In vivo/in vitro evaluation of FDDS has been discussed by
scientists to accesess the efficiency and application of such systems. Several
recent examples have been reported showing the efficiency of such systems for
drugs with bioavailability problems.
Approaches to Design Floating Dosage Forms
The following approaches have been used for the design of floating dosage
forms of single and mahipt unit system, 13
Figure 1: Intragastric residence positions of floating and non-floating units.
Advantages of FDDS:
1. The Floating systems are advantageous for drugs meant for local action in the
stomach. e.g., antacids.
2. Acidic substances like aspirin cause irritation on the stomach wall when come
in contact with it Hence FDDS may be useful for the administration of aspirin
and other similar drugs.
3. Administration of prolongs release floating dosage forms, tablet or capsules,
will result in dissolution of the drug in the gastric fluid. They dissolve in the
gastric fluid would be available for absorption in the small intestine after
emptying of the stomach contents.
5. It is therefore expected that a drug will be fully absorbed from floating
dosage forms if it remains in the solution form even at the alkaline pH of the
intestine.
Disadvantages of FDDS:
1. Floating system is not feasible for those drugs that have solubility or stability
problem in G.I. tract.
2. These systems require a high level of fluid in the stomach for drug delivery to
float and work efficiently.
3. Drugs showing absorption window at stomach region are only considered to
be better candidates.
Drug Candidates Suitable for FDDS:
1. Drugs that have narrow absorption window in GIT (e.g., L-DOPA, p-amino
benzoic acid, furosemide, riboflavin) 14.
2. Drugs those are locally active in the stomach (eg, misoprostol, antacid) 15
3. Drugs those are unstable in the intestinal or colonic environment (e.g.,
captopril, ranitidine HCI, metronidazole) 16
4. Drugs that disturb normal colonic microbes (e.g., antibiotics used for the
eradication of
Helicobacter pylori, such as tetracycline, clarithromycin, amoxicillin) 17
5. Drugs that exhibit low solubility at high pH values (e.g., diazepam,
chlordiazepoxide) 18.
Applications of Floating Drug Delivery Systems
Floating drug delivery offers several applications for drugs having poor
bioavailability because of the narrow absorption window in the upper part of the
gastrointestinal tract. It retains the dosage form at the site of absorption and thus
enhances the bioavailability. These are summarized as follows.
Sustained Drug Delivery
HBS systems can remain in the stomach for long periods and hence can release
the drug over a prolonged period of time. The problem of short gastric residence
time encountered with an oral CR formulation hence can be overcome with
these systems. These systems have a bulk density of GI as a result of which they
can float on the gastric contents. These systems are relatively large in size and
passing from the pyloric opening is prohibited.
Recently sustained release floating capsules of nicardipine hydrochloride were
developed and were evaluated in vivo. The formulation compared with
commercially available MICARD capsules using rabbits. Plasma concentration
time curves showed a longer duration for administration (16hours) in the
sustained release floating capsules as with conventional MICARD capsules
(8hours).
Similarly, a comparative study between the Madopar HBS and Madopar
standard formulation was done and it was shown that the drug was released upto
8 hours in vitro in the former case and the release was essentially complete in
less than 30 minutes in the latter
case.
Site-Specific Drug Delivery
These systems are particularly advantageous for drugs that are specifically
absorbed from stomach or the proximal part of the small intestine, eg, riboflavin
and furosemide. Furosemide is primarily absorbed from the stomach followed
by the duodenum. It has been reported that a monolithic floating dosage form
with prolonged gastric residence time was developed and the bioavailability was
increased. AUC obtained with the floating tablets was approximately 1.8 times
those of conventional furosemide tablets 20
A bilayer floating capsule was developed for local delivery of misoprostol,
which is a synthetic analog of prostaglandin El used as a protectant of gastric
ulcers caused by administration of NSAIDS. By targeting slow delivery of
misoprostol to the stomach, desired therapeutic levels could be achieved and
drug waste could be reduced.
