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Bioadhesion: It is the term that describes the adhesion of a polymer to a biological substrate.
When the adhesion is restricted to the mucus layer lining of the mucosal surface it is termed as mucoadhesion. The mucosa lines a number of regions of the body including the gastrointestinal tract, the urogenital tract, the airways, the ear, nose, and eye. These represent potential sites for attachment of any mucoadhesive system and hence, the mucoadhesive drug delivery system may include the following: 1. Buccal delivery system 2. Nasal delivery system 3. Ocular delivery system 4. Transdermal delivery system
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The buccal mucosa is highly perfused with blood vessels and offers a greater permeability than the skin. Termination of therapy is easy.
Disadvantages: Not suitable for drugs with unpleasant taste ,odour or which irritate the oral mucosa Only drugs with small dose requirements can be administered. Eating and drinking may become restricted. Drugs which are unstable at buccal pH cannot be administered by this route. Only those drugs, which are absorbed by passive diffusion, can be administered by this route Swallowing of the formulation by the patient may be possible Over hydration may lead to the formation of slippery surface and structural integrity of the formulation may get disrupted by the swelling and hydration of the bioadhesive polymers.
Bioadhesive dosage forms designed for buccal drug delivery includes: a) b) c) d) Buccal tablets Patches films gels and in-situ gel.
by approximately 300 microvilli, which greatly increase the surface area of the nasal cavity. The lamina propria, below the epithelium, houses blood vessels, nerves, and both serous and mucus secretory glands. Blood is delivered to the nose from the external and internal carotid arteries. The lamina propia contains a dense network of capillaries. A mucus layer, resulting from nasal and lacrimal gland secretions as well as plasma transudate, is present on the nasal passage epithelium. The pH of secretions ranges from 5.5 to 6.5 and from 5.0 to 6.7 in adults and children, respectively. The mucus consists of an outer viscous layer of mucus (gel) and a watery (sol) layer located along the mucosal surface. Glycoproteins, particularly mucin, are responsible for the gel-like appearance of the mucus. Lysozymes, enzymes, and immunoglobulins in addition to other proteins may also be found in the mucus. Approximately 3% of the mucus consists of these proteins while the remainder is made of 9095% water and 12% salt.
Advantages of Nasal Drug Delivery System: Drug degradation that is observed in the gastrointestinal tract is absent. Hepatic first pass metabolism is absent. Rapid drug absorption and quick onset of action can be achieved. The nasal route is an alternative to parenteral route, especially for protein and peptide drugs.
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Rapid onset of action. Ease of administration, non-invasive. Minimal aftertaste Self administration
Disadvantages of Nasal Drug Delivery System: Nasal administration is primarily suitable for potent drugs since only a limited volume can be sprayed into the nasal cavity. Drugs for continuous and frequent administration may be less suitable because of the risk of harmful long term effects on the nasal epithelium.
Bioadhesive dosage forms for nasal delivery includes: a) b) c) d) e) Gels Sprays and aerosols Powders In-situ gel Microspheres.
pathways. All these protective mechanisms are responsible for te rapis and extensive procorneal loss of topically applied ophtalmic drugs.
Fig 3. Eye Advantages of ocular drug delivery: Local drug delivery in case of ocular diseases like glaucoma. Drug delivery for treating the ocular infections.
Disadvantages of ocular drug delivery: Less capacity of cualdy sac (up to 7.5lit) Dilution of drug due to lachrymal secretion. Nasolachrymal drainage Bioadhesive dosage form designed for ocular drug delivery: a) b) c) d) In-situ gel Ocusert Gels and ointments containing liposomes and nanoparticles Inserts
The main functions of the skin are protection against dessication and injury an plays an important role in thermo regulation and water balance. Two principal layers are distinguished: the epidermis which is the surface layer and the dermis or cornium, which is a subadjacent connective tissue layer. The principal cell of the skin is the keratinocyte. It is stacked in several layers to form the keratinized squamous stratified epithelium. The layers are stratum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum. Fig. 4. Skin
The dermis consists of a matrix of connective tissue woven from fibrous proteins(collagen, elastin and reticulin) that are embedded in an amorphous ground substance of mucopolysaccharide. Nerves, blood vessels and lymphatics traverse the matrix and skin appendages (eccrine sweat glands and pilosebaceous glands) pierce it. The dermis needs an efficient blood iarrh to convey nutrients, remove waste products, regulate pressure and temperature and contribute to skin colour. Advantages of topical drug delivery:
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Provides large surface area. It avoids first pass metabolism and gastrointestinal irritation. Non-invasive method of drug administration. Self administration. Suitable in instances like vomiting/ iarrhea where oral route is not desirable. Therapy can be quickly terminated by removal of the patch from the skin. Less chances of over or under dosing as the result of prolonged preprogrammed delivery of drug at the required therapeutic rate.
Disadvantages of topical drug delivery system: Suitable for drug having sufficiently low molecular weight Onset of action is delayed Transdermal drug delivery systems could be unsuitable for drugs that irritate or sensitize skin
Bioadhesive dosage form designed for transdermal drug delivery includes: a) Metered dose transdermal spray b) Transferosomes, liposomes, etc 5) Gastrointestinal Drug Delivery: Anatomy and Physiology: Basically the entire GIT from mouth to rectum is made up of 4 different layers: serosa, muscularis mucosa, submucosa and mucosa. The pH of gastric fluid varies from 1-3.5 depending on the fasting or fed state. Stomach has 3 parts: fundus, body and pylorus. The epithelium of stomach consists of columnar cells which are covered with the protective mucus layer. The surface of the epithelium is pierced by the openings of gastric glands which are responsible for the secretion of hydrochloric acid and other digestive enzymes.
Fig. 5 Gastrointestinal tract Advantages of gastrointestinal drug delivery: For the delivery of drugs used in treatment of local diseases of stomach like acidity, H.pylori infection. Improvement in the bioavailability of drugs having absorption window in the stomach or those which are degraded in the intestinal pH.
Disadvantages of gastrointestinal drug delivery: Due to constant renewal of mucus layer, retention of bioadhesive dosage form is difficult. Not suitable for drugs that might produce gastric lesions like NSAIDs.
Bioadhesive dosage forms for gastrointestinal drug delivery includes: a) In situ floating gels b) Bioadhesive tablets and capsules c) microparticulate systems including microspheres, nanoparticles, pellets, etc
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cellularity, and albumin concentration, with potential effects on drug delivery. Since vaginal fluid is aqueous in nature, it follows that any drug intended for systemic absorption via the vaginal epithelium will require a degree of aqueous solubility.
Advantages of vaginal drug delivery: Large surface area Good blood supply The ability to bypass first pass liver metabolism Permeability to large molecular weight drugs such as proteins and peptides. Prolongs the residence time
Disadvantages of vaginal drug delivery: Drug absorption is highly dependent on the thickness of the epithelium which in turn is dependent on the phase of menstrual cycle.
Bioadhesive dosage forms designed for vaginal drug delivery includes: a) Mucoadhesive hydrogels b) microspheres formulated using bioadhesive polymers c) SuperVailTM vaginal gels(In SupraVail gels, the phospholipid adopts a liquid crystalline matrix and forms a bilayered translucent gel. On contact with the mucosal surface, the bilayered gel formulation converts readily in vivo to vesicular structures.) d) Bioadhesive vaginal cream based on VagiSiteTM technology( cream containing high internal phase ratio, w/o emulsion. After introduction of the drug-containing emulsion to a mucosal surface, in this case the vaginal mucosa, a thin bioadhesive film of contiguous drug-laden internal-phase globules forms on the mucosal surface).
excretion via hepatic mechanisms. The rectal cavity is also drained by extensive lymphatic circulation which facilitates absorption and systemic exposure of absorbed drugs. Although extensive villi and microvill are not present in the rectum and colon, sufficient surface area is present to allow absorption of readily permeable drugs. The lack of motility in the rectum and colon, as opposed to extensive motility in the small intestine, provides and additional advantage in terms of maintaining maximum concentration gradients at the absorptive surface. Together with a limited fluid volume in the lower colon, typically 2-3 ml of inert mucus fluid in the absence of fecal material, the static environment of the rectum and lower colon provides an area for maintaining significantly higher drug concentrations than readily achievable in the small intestine. Advantages of rectal drug delivery: Large surface area. The ability to bypass first pass metabolism. Prolongs the residence time Permeability to large molecular weight drugs, such as peptides and proteins.
Bioadhesive dosage forms designed for rectal drug delivery mainly includes: a) Gels and creams b) microspheres
References:
Michael J. Rathbone, J Hadgraft, M.S. Roberts, Modified-Release Drug DeliveryTechnology, Marcel Dekker, Inc, Pg No:728-729,760-764. James Swarbrick, Encyclopaedia of Pharmaceutical Technology,3rd edition, Informa Healthcare, Pg No: 1300-1301. www.pharmainfo.net Punitha S, Girish Y, Polymers in muchadhesive buccal drug delivery system-A review, Int. J. Res.Pharm.Sci. Vol-1, Issue-2,170-186,2010
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