An Overview on: Sublingual Route for Systemic Drug Delivery

More documents

Recommendations

Info

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701order to keep the tablet in place. Swallowing ofsaliva should also be avoided since the saliva maycontain dissolved drug. Bland excipients are usedto avoid salivary stimulation. Various techniquescan be used to formulate rapidly disintegrating ordissolving tablets. (12,13) Direct compression is oneof these techniques which require incorporation ofa superdisintegrant into the formulation, or the useof highly water-soluble excipients to achieve fasttablet disintegration. Direct compression does notrequire the use of water or heat during theformulation procedure and is the ideal method formoisture and heat-labile medications.a) Fast disintegrating sublingual tablets (FDT)FDT is defined as a solid dosage form that containsmedicinal substances and disintegrates rapidly(within few seconds) without water when kept onthe tongue. The drug is released, dissolved, ordispersed in the saliva, and then swallowed andabsorbed across the GIT (14) . FDTs also are alsocalled as Orodispersible tablet, mouth-dissolving,quick-dissolving, fast-melt, and freeze-driedwafers. Tablets that disintegrate or dissolve rapidlyin the patient’s mouth are convenient for youngchildren, the elderly and patients with swallowingdifficulties and in situations where potable liquidsare not available. Direct compression is one of thetechniques which require the incorporation of asuperdisintegrant into the formulation, or the use ofhighly water soluble excipients to achieve fasttablet disintegration. Compared to conventionaldosage form the drug dissolution, its absorption aswell as onset of clinical action and itsbioavailability may be significantly greater (15-17) .Though chewable tablets are available in themarket, they are not same as the new FDTs.Patients for whom chewing is difficult or painfulcan use these FDTs. It can be used easily in infantsand in children who have lost their primary teethand who do not have full use of their permanentteeth (18) .Recent market studies indicate that more than halfof the patients prefers FDTs than otherconventional dosage forms (19) and most patientswould ask their doctors for FDTs (70%), purchaseFDTs (70%), or prefer FDTs than regular tablets orliquids (>80%) (20) . The US Food and DrugAdministration Center for Drug Evaluation andResearch (CDER) defines, in the „Orange Book ,an FDT as “a solid dosage form containingmedicinal substances, which disintegrates rapidlyin saliva, usually within a few seconds, whenplaced upon the tongue” (21). The implication ofthese dosage forms is emphasized by the term“Orodispersible Tablet”, by the EuropeanPharmacopoeia which defines it as a tablet that canbe placed in oral cavity where it disperses rapidlybefore swallowing (22) . FDTs has been developedfor numerous indications ranging from migraines(in which quick onset of action is necessary) tomental illness (in which patient compliance isnecessary for treating chronic indications such asmental depression and schizophrenia) (23) .b)Bioadhesive sublingual tabletsThe new sublingual tablet concept presented isbased on interactive mixtures consisting of a watersoluble carrier covered with fine drug particles anda bioadhesive component. With this approach, it ispossible to maintain rapid dissolution incombination with bioadhesive retention of the drugin the oral cavity. Bioadhesion is usually defined asthe bond formed between two biological surfacesor between a biological and a synthetic surface.Problem associated with sublingual tabletformulation is that there is always a risk that thepatient will swallow part of the dose before theactive substance has been released and absorbedlocally into systemic circulation. this could resultsan unwanted prolongation of the pharmacologicaleffect. Addition of a bioadhesive component is awell-known method of increasing the possibility ofa more site-specific release. However, this conceptis normally applied to non-disintegrating tablets ordisc to achieve extended release of the activesubstance and, consequently, such a system will notbe suitable for a fast acting formulation. Therefore,it would be of interest to study a disintegratingtablet which releases the drug quickly, but whichalso has bioadhesive properties which couldprevent the drug from being swallowed.Bioadhesion mechanismsThe mucus layer is often involved in the adhesionof a bioadhesive polymer and is present as either agel layer adhering to the mucosal surface or asolution or suspension of various substances. Themucus layer mainly consists of mucin glycoprotein,Vol. 3 (2) Apr – Jun2012 www.ijrpbsonline.com 916
International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701inorganic salts, proteins, lipids and water with thecomposition varying depending on its source. Theelectronic theory involves an electronic transferbetween the two materials causing a double layerof electric charge, which results in attraction forces.The adsorption theory involves adhesion betweenthe mucosa and the adhesive material by van derwaals interaction, hydrogen bonds and relatedforces. The wetting theory involves interfacialtensions between the two materials. Penetration ofthe polymer chains into the mucus network andvice versa, causing a mechanical bond, is referredto as the diffusion theory. The importance of watercontent and movement of water into the adhesivematerial from the mucosa, i.e. dehydration of themucosa, has also been suggested as a mechanicalfor adhesion.Measurement of bio-adhesive strengthBio-adhesion strength of the tablets was measuredon a modified physical balance. The method usedbovine cheek pouch as the method mucosal andIPB ph 6.6 as the moistening fluid. The surface ofthe mucosal membrane was first blotted with afilter paper and then moistened with 25/L 1 of IPBpH 6.6. the weight in grams is required to detachthe tablets from the mucosal surface gave themeasure of bio-adhesive strength.c) Lipid matrix sublingual tabletsSuch tablets are formulated using advances insublingual and liposomal technology to create adosage form that offers a faster and more completeabsorption than traditional oral routes ofadministration. The lipid matrix sublingual tablet isa bioavailable, quick, convenient and consistentdosage form for many neutraceuticals that are oftentaken orally.For e.g., Glutathione MB12(methylcobalamin)melatonin.d) Sublingual vitamin tabletVitamin D i.e. cholecalciferol is a natural precursorof calcium regulating hormone calcitriol. VitaminD is thus used in hypocalcaemia/hyperparathyroidism. Because of its incompleteabsorption from GI tract, local intestinaldegradation and hepatic metabolism, it is givensublingually.2)Thin film drug deliveryThin film drug delivery is a process of deliveringdrugs of the systemic circulation via thin film thatdissolves when in contact with liquid, oftenreferred to a dissolving films or strips and dissolvewithin 1 min when placed in the mouth withoutdrinking or chewing.Such dissolving film or strip are typically designedfor oral administration, with the user placing thestrip on or under the tongue or along the inside ofthe cheek. Thin film’s ability to dissolve rapidlywithout the need for water provides an alternativeto patients with swallowing disorders and topatients suffering from nausea, such as thosepatients receiving chemotherapy.The first developed fast-dissolving dosage formconsisted in tablet form, and the rapiddisintegrating properties were obtained through aspecial process or formulation modifications 24 .More recently, fast-dissolving films are gaininginterest as an alternative to fast-dissolving tablets todefinitely eliminate patients’ fear of chocking andovercome patent impediments. Fast-dissolvingfilms are generally constituted of plasticizedhydrocolloids. Problems are caused by foamingduring the film formation due to the heating of thematerial or solvent evaporation, the flaking duringthe slitting and the cracking in the cutting phase.The films should be stable to moisture, facilitatethe handling, have to be flexible and exhibit asuitable tensile stress and do not stick to thepackaging materials and fingers.Film can be prepared by five method: 1) Solventcasting. 2)Semisolid casting. 3)Hot melt extrusion.4)Solid dispersion extrusion. 5) Rolling.1) Solvent casting methodFilm is formulated using the solvent castingmethod, whereby the water-soluble ingredients aredissolved to form a clear viscous solution. The APIand other agents are dissolved in smaller amountsof the solution and combined with the bulk. Thismixture is then added to the aqueous viscoussolution. The entrapped air is removed by vacuum.The resulting solution is cast as a film and allowedto dry, which is then cut into pieces of the desiredsize. 252)Semisolid castingSolution of water soluble film forming polymer ismixed with solution of acid insoluble polymerwhich forms homogenous viscous solution. Theratio should be 1:4. For e.g. cellulose acetatephthalate, cellulose acetate butyrate. It is thensonicated which is coated on non-treated castingfilm.3)Hot Melt ExtrusionIn present method the mass is prepared first underthe control of temperature and steering speed.Afterwards, the film is coated and dried in a dryingtunnel, once again the temperature, air circulationand line speed are controlled. Then follows aslitting and in the last step the films are punched,pouched and sealed. 264)Solid Dispersion ExtrusionSolid dispersions are prepared by immisciblecomponents and drug. Finally the solid dispersionsare shaped in to films by means of dies.5)RollingSolution or suspension drug is rolled on the carrier.The solvent is mainly water and mixture of waterVol. 3 (2) Apr – Jun2012 www.ijrpbsonline.com 917
Page 3: International Journal of Research i
Page 7 and 8: International Journal of Research i
Page 9 and 10: International Journal of Research i
Page 11: International Journal of Research i

An Overview on: Sublingual Route for Systemic Drug Delivery

Create successful ePaper yourself

Delete template?

Save as template?