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Rectalsuppositoryasaneffectivealternativefororaladministration

ARTICLEinRESEARCHJOURNALOFPHARMACYANDTECHNOLOGY·JUNE2015

DOI:10.5958/0974-360X.2015.00122.5

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used combination of xanthan gum and sodium alginate ina hydrophilic and lipophilic polymer base5. They foundthat suppositories containing xanthan -alginatemicrospheres is an effective alternative to oral dosageforms as it sustains the GH release, avoids first passmetabolism, and can be efficiently used in themanagement of emesis in cancer chemotherapy andradiation therapy. But now days a variety of natural andsynthetic drugs are formulated in the form ofsuppositories to produce a systemic effect such ashypnotics, tranquilizers, antispasmodics, etc. Also, thesuppository may be useful as a sustained releaseformulation for the long treatment of chronic diseasessuch as hypertension, asthma, diabetes, anemia, AIDS,etc6. Mokhtar and coworkers developed antihypertensivesuppositories of atenolol in hydrophilic bases ofpolyethylene glycol (PEG), or hydrophobic emulsifyingbases such as witepsol H15 (WH15) nonionic surfactantspan 60 (Sp 60) with or without cholesterol (CH) andHPMC 400Cp7. They found that the arterial bloodpressure lowered in six hours and persisted at normallevels within 6 h.

Further, suppositories have application in post operativepains. Therefore, administration of medicaments in theform of suppository is the preferable route ofadministration due to the advantages that include: a)improved enzymatic drug stability b) higher drug contentc) constant and static environment of rectum d)avoidance of overdosing e) improved patient compliancef) avoidance of first pass elimination8.

A conventional suppository is a semisolid dosage formmeant for insertion into body cavity that melts or softensat body temperature. It is acceptable dosage form forinfants, children and unconscious patients. A majoradvantage of suppositories over oral dosage forms is thatit does not undergo the first pass effect in thegastrointestinal tract and liver. However, theconventional solid suppositories suffer fromdisadvantages such as feeling of alien, discomfort andtherefore, refusal by the patient. If such solidsuppositories without mucoadhesivity reach the end ofcolon, drugs may undergo the first-pass effect. Theproblem of conventional solid suppositories can beovercome by developing a liquid suppository which: (1)forms a gel at body temperature; (2) has a suitable gelstrength not to be leaked out from the anus afteradministration; and (3) has a suitable bioadhesive forceso as not to reach the end of the colon9. Choi andcoworkers fabricated ibuprofen loaded liquidsuppository using eutectic mixture system with mentholand poloxamer P 188 as a base and noted that theeutectic mixture with menthol improved the solubility ofibuprofen and such suppositories could be inserted intothe rectum of rats without difficulty and leakage10.Further, they suggested that drug from liquid suppository

could be more absorbed than that from solid one in rats.Mucoadhesive polymers have recently gained interestamong pharmaceutical scientists as a means ofimproving drug delivery by promoting residence timeand contact time with the mucous membranes. Barkatdeveloped and evaluated rectal etodolac poloxamer gelsystem composed of poloxamer and bioadhesivepolymers11. They concluded that in situ gellingsuppository with etodolac and mucoadhesive polymerssuch as microcrystalline cellulose and carbopol was safe,convenient and effective dosage form of etodolac. In thisreview, attempts are made to discuss effectiveadministration of drugs. It focuses on rectalbioavailability of drugs, factors influencingbioavailability, role of surfactant and mucoadhesivepolymers in enhancing bioavailability. It also highlightson suppository bases, evaluation parameters for solid andliquid suppositories.

BIOAVAILABILITY OF DRUGS FROMSUPPOSITORIES:I) Physiology and biopharmaceutical characteristicsof rectum:Human colon consists of ascending, descending,transverse and sigmoid colon. Sigmoid colon turnsmedially and downward into the rectum and anal canal.The rectum is about 13 cm long and the anal canal is offew centimeters of the colon that surrounds the anus. Theterminal end of colon is usually referred as rectumclinically12. The rectum has relatively small absorptionsurface 0.02-0.05m2 and is characterized by absence ofvilli13. Viscous rectal fluid (0.5 - 1.25ml) spread overthe surface having pH 7.4 with a low buffer capacity.The rectum is usually empty except when fecal matterarrives from higher part of the colon temporarily. Thismaterial is either expelled or transported back into colon,depending on the voluntary control exhibited by the anussphincter. A drug has greater opportunity to makecontact with the absorbing rectal surface in the absenceof fecal matter. Other conditions such as diarrhoea,colonic obstruction and tissue dehydration can influencethe rate and degree of drug absorption from rectal site14.Absorption of drug from rectal suppositories depends ondiffusion of drug to the site of rectal mucosa. Thediffusivity of drug depends on nature of drug andphysiological state of the colon that is amount andchemical nature of fluids and solids present. The rectumis usually empty except when fecal matter arrives fromhigher part of the colon temporarily. This material iseither expelled or transported back into colon, dependingon the voluntary control exhibited by the anus sphincter.A drug has greater opportunity to make contact with theabsorbing rectal surface in the absence of fecal matter.Other conditions such as diarrhoea, colonic obstructionand tissue dehydration can influence the rate and degreeof drug absorption from rectal site. Rectal administrationof drug avoids partly hepatic first-pass elimination. The

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superior rectal vein and middle rectal vein are connectedto the portal system and inferior rectal vein is directlyconnected to inferior vena cava thus entering drug intothe systemic circulation15. However, there is no sharpdistinction between these venous drainages, since therectal veins are linked by an extensive anastomosesnetwork. With this route, 50-70% of a drug suitable forrectal administration is absorbed. In one study, it wasobserved that on lidocaine, avoided hepatic first-passelimination following rectal administration of the drug16.Systemic availability was found to be increased byalmost 100% following rectal administration comparedwith the oral route for the same dose. The absorption ofdrug through rectal administration is related with pHpartition theory. Thus, rectal absorption involves simplediffusion process through the lipoidal membrane.

Physico-chemical and physiological properties may haveinfluence on permeability of drugs across the intestinalepithelium and may differ in various intestinal regions17.Permeability of drug across the rectum depends onmucosal area, fluid volume and pore size. In rectum,absorption of water is low as compared to other parts ofthe gastrointestinal tract18. This is due to smaller poreradius, tighter epithelium, less fluidity in the rectalmembrane, lower number of pores in the rectal region,and decreased mucosal surface area. There is adifference in the transport of electrolytes and water.These are transported transcellularly in the colon/ rectumthat is different from more high permeable tissue inwhich the transportation of electrolytes takes place bythe paracellular route13. It was observed that an unstirredwater layer is an essential factor as it may be thick andmore coherent in the colonic-rectal region in the jejunumof human.

In suppository where drug substance dissolves ordisperses in the vehicle, the absorption may depend onthe particle size, solubility in water and partitioncoefficient. In other cases where drugs dissolve eitherfully or in parts in base the absorption will depend onsolubility in the base, water distribution coefficient andrelative phase volume ratio19. According to Kakemi,drug may be absorbed only when it is dissolvedcompletely in aqueous rectal fluid as there is a littleabsorption of drug from the oily solution.

If M0 is the amount of drug in oil and Mw is amount ofdrug in water and Ø is a relative phase volume ratio, thenthe release of drug from suppository will be representedby the following equation

Mw = M0/ (K Ø)

Where K is the partition coefficientAbove equation describes the equilibrium conditions. Ifthe rate of partioning of drugs is slower than the

absorption from aqueous phase, equilibrium will neverbe reached. In such situation, rate determining processwill be transfer of drug from oil to water. Hence, for invitro drug release sink conditions should be maintained.The larger volume of dissolution medium will berequired for transportation of dissolved drug frommolten mass so that it will provide an adequate area ofcontact between two phases in order to make releasekinetics to in vivo. A fat-like base should be used for awater-soluble drug and a hydrophilic base for waterinsoluble drug. Diffusion rate of a drug suspended in afat base having low hydroxyl number and viscosity isincreased.

II) Pharmaceutical aspects related to bioavailability:Rectal absorption of drug through suppository involves achain of effects leading to the bioavailability of the drug.The sequence of such drug absorption from the anorectalarea can be represented as follows:

Drug in vehicle Drug in colon fluidsAbsorption through the rectal mucosa

Drugs should be released from suppository anddistributed by surrounding fluids to the sites ofabsorption so that it will be available for absorption. Asuppository will either dissolve in the rectal fluid (water-soluble bases) or melt on the mucous layer (fatty bases)depending on the character of its vehicle.

i) Particle size, solubility in water and interfacialtension:Drug absorption by rectal route is governed by particlesize, solubility in water and interfacial tension. Processof release of drug from suppository involves the varioussteps such as melting, spreading, sedimentation, wettingand dissolution19, 20. Usually, absorption of drug dependson the rate of dissolution which is related to the particlesize. Smaller the particle size better will be theabsorption as smaller particle size increases the surfacearea which increases the rate of dissolution. Insuppository, drug should have particle size less than50µm. In suppository, though the smaller particle size ofdrug does not increase the blood levels but for itsdissolution in the rectal fluid requires smaller particlesize. For the release of an insoluble drug from vehicle,larger particles of drug which are soluble in the rectalfluid will be preferred to increase its transport rate.

Surface properties of the drug particles is an importantconsideration in evaluation of rate of drug release asdrug particles in suppository dosage form transfers fromone phase to another. If drug particles do not wet in thevehicle or base, it may agglomerate, which in turn mayaffect the uniformity of dispersion of drug particles. Itmay occur due to the increased tendency for theagglomerated powder to sediment prior to the setting of

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suppository. Therefore, it is necessary to add surfactantto formulation to reduce the surface effects of poorlywettable drug particles and to improve the wetting ofdrug particles that will facilitate dissolution of drug inthe suppository and in rectal fluids.

ii) Hardening effect:Hardening effect leads to increase in the melting time ofsuppositories. It occurs during storage of suppositories.This effect arises in bases with higher melting ranges(Witepsol H37, 36-38°C). Minor changes occur in baseswith the lowest melting points (e.g. Witepsol H 32, 31-32 ° C). It can be inhibited by the addition of 2% soyalecithin. It is considered that hardening effect occurs dueto polymorphic phase transitions, increase in crystallinityand transesterification. Crystallization of polymorphscan be prevented by blending suppository bases withsurface-active agents in optimum concentrations as athigher surface-active agent concentrations produceretardant and/or irritative effects. Varnshey andcoworker studied effect of different surfactants such assodium lauryl sulphate, span 60 and 80, tween 60 and 80and sodium tauchocholate on the release pattern of cocoabutter suppository containing flurbiprofen sodium21.They observed that on addition of surface active agentsto the formulation enhanced the drug release with respectto surfactant which can be arranged as- SLS > Span 80 >Tween 80 > Tween 60 > Sodium taurocholate > Span 60> cocoa butter.

Suppository basesSuppository bases must melt, soften or dissolve in orderto facilitate or promote the release of drug in such waythat it is readily available for absorption8. A chemicaland/or physical interaction between drug and base mayinfluence the stability and/or bioavailability of drug.Potential chemical and/or physical interactions betweena drug and the components of a formulation should beinvestigated during preformulation studies and in theearly stages of formulation development. The base mayirritate mucous membranes and initiate a colonicresponse thus promoting unwanted bowel movementsresulting in the expulsion of the dosage form, therebynegating any potential drug absorption via the rectalroute. The spreading of suppository base with asuspended drug in the recto colon is dependent on thepressure exerted through rectal wall by abdominalorgans and/or by rectal wall muscles. The final spreadingarea decreases with increasing apparent viscosity of thespreading system20.

There are two types of suppository bases, oleaginousbases and water miscible bases.

Oleaginous basesFatty bases melt at body temperature. Cocoa butter (CB)is the most commonly used oleaginous suppository basebut it poses several technical challenges with respect tothe manufacture of dosage forms of suitable quality19. Ithas several disadvantages such as it can become ranciddue to oxidation of the unsaturated glycerides, melt inwarm weather and liquefy when incorporated withcertain drugs. It does not contain emulsifiers andtherefore does not take up large quantities of water. AsCB can easily melt and become rancid, it must be storedin cool, dry place and protected from light. CB exhibitsmarked polymorphism (the ability to exist in differentcrystalline forms, namely α, β, β’ and γ), a phenomenonprobably attributed to the high proportion of unsaturatedtriglycerides22. The most stable β form is preferable forsuppositories. The formation of the various crystallineforms depends on the conditions and degree of heatingand cooling. Prolonged heating above 36oC leads to theformation of the unstable crystal with lower meltingpoints. Lo and coworkers formulated thermogelling andbioadhesive liquid suppositories of epirubicin usingvarying concentrations of polyacylic acid (PAA) andpluronic23. Also, they prepared solid suppositories usingthe same concentrations of PAA and pluronic in cocoabutter base. They found that solid suppositories preparedwith cocoa butter base melted and gelled instantly in therectum. It remains adhered to the mucous membrane andsustained release of drug. Further, they stated that cocoabutter has antioxidant property, which granted it astorage life of two to five years and thus protected theenclosed Plu/PAA/Epi mixture.

Semi-synthetic fats are usually white, brittle, solid,odorless and unctuous to touch and producesuppositories that are white and have an attractive, clean,polished appearance. Hard fats are available in a varietyof grades with different melting ranges, hydroxyl valuesand other physicochemical characteristics. Examples ofsemi-synthetic fatty suppository bases that are availablecommercially include fractionated palm kernel oil B.Pand hard fats such as Massa Estarium®, Massupol®,Suppocire® and Witepsol®. Kamalinder S et al.,developed suppocire based solid suppositories ofparacetamol with the help of additives such as sodiumlauryl sulfate (SLS), dioctyl sulfosuccinate (DOSS),Labrasol, lecithin, Miglyol 812, aerosil, Capryol PGMC(CPGMC) and span 80 and they found that addition ofDOSS and aerosil showed prolonged drug releasewhereas newly used Labrasol and C PGMC exhibitedmuch faster release24.

Water miscible basesMacrogol or polyethylene glycols (PEGs) are amongstthe most widely used hydrophilic polymer suppositorybases. PEGs are polymers of ethylene oxide and water,prepared in a variety of chain lengths, molecular weights

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and physical states25. PEGs with a molecular weightranging between 200 and 600 exist as liquids and, as themolecular weights increase to above 1000; they exist aswax-like solids26. In addition, as the molecular weightsincrease, their water solubility and hygroscopicitydecreases. The wide range of melting points andsolubilities make possible the formulation ofsuppositories with various degrees of heat stability andwith different dissolution rates. PEGs of differentmolecular weight can be combined to achieve asuppository base of desired consistency and that canachieve a specific drug release rate profile. The use ofhigh melting point solids as suppository bases permitsconvenient storage of the suppositories without the needfor refrigeration and without the danger of excessivesoftening in warm climates. PEGs have inherently goodsolvent properties that may result in the retention of adrug in the liquefied base, in the rectum with thepotential for a reduction in therapeutic activity. If thedrug is partly in solution and partly in suspension there isa high potential for crystal formation, which may causethe formulation to become brittle and prolong dissolutiontime. PEG bases are hygroscopic and therefore attractwater, resulting in a painful sensation for the patient. It istherefore recommended that suppositories manufacturedfrom these bases should be moistened with water prior tointroduction into rectum to minimize local irritation.PEG bases have several advantages over synthetic andsemi-synthetic suppository bases, in particular withrespect to stability against oxidation and otherdegradation processes, their inert nature and a high waterabsorbing capacity. Unlike glycerol-gelatinsuppositories, PEG suppositories do not adhere tomoulds and contract sufficiently on cooling to makemould lubrication unnecessary during manufacture.However, PEG suppositories may become brittle, unlesspoured at the lowest temperature possible, but this maybe overcome or reduced by the addition of surfactants orplasticizing agents such as propylene glycol to theformulation. Tarimici N et al., prepared witepsol H15and PEG mixture (PEG 400, PEG 1000, PEG 2000 andPEG 4000) based indomethacin sustained release solidsuppositories using cellulose acetate phthalate andEudragit RL and RS in 1:1 ratio and they found thatformulations containing combinations of PEG 400 andPEG 4000 as well as PEG 1000 and PEG 4000 andEudragit mixture exhibited sustained release effect27.

SurfactantsSurfactants can increase and decrease drug absorptionrate. For instance, in case of sodium iodide, absorption isaccelerated in the presence of surfactants and appears tobe proportional to the relative surface tension loweringof the vehicle. Riegalman and Crowell showed that therate at which drug diffuses to the surface of suppositorydepends on the particle size of suspended drug and thepresence of surface active agents that affect drug release

from suppositories28. In addition, they suggested that theacceleration of sodium iodide absorption might also beattributed to the mucus peptizing action of the vehicle.The rectal membrane is covered by a continuous blanket,which may be more readily washed away by colonicfluids that have reduced surface tension. The cleansingaction caused by the surfactant-containing vehicle maymake additional pore spaces available for drugabsorption, thus facilitating drug movement across therectal membrane barrier. In case of phenol-type drugs,absorption rate is decreased in the presence of surfactant,probably because of the formation of a drug surfactantcomplex26.

Several nonionic surface active agents, closely relatedchemically to the polyethylene glycols, have beendeveloped as suppository bases29. Many of these basescan be used for formulating both water soluble and oilsoluble drugs. The most commonly used surfactants insuppository formulations are the polyoxyethylenesorbitan fatty acid esters (tween), polyoxyethylenestearates (Myrj), and the sorbitan fatty acid esters (Spanand Arlacel). Caution should be taken while usingsurfactants with drugs. It has been reported thatsurfactants increased rate of drug absorption30, 31. Otherreports suggested interaction of surface active agentswith drugs that may lead to decrease in therapeuticactivity32. Each formulation must be tested in vivo toevaluate its medicinal effectiveness, as well as safety.Gross and Becker recommended a water dispersible,high melting point (500 C) suppository base consisting ofpolyoxyethylene 30 stearate (Myrj 51), water, white waxand dioctyl sodium sulfosuccinate (Aerosol OT)33. Theuse of aerosol OT in the formula was claimed to lendsynergism to the surfactant and thus aid in rapiddisintegration of suppository. Drugs like phenobarbital,quinine hydrochloride, tannic acid, and chloramphenicolwere studied. Ward designed suppositories usingpolyoxyethylene sorbitan derivatives (Tweens) to melt atbody temperature into liquids that disperse readily in thebody fluids 34.

Poloxamer is used as a base for liquid suppositories.Being non ionic surfactant, it is a copolymer of poly(oxyethylene)-poly (oxypropylene)- poly(oxyethylene.Poloxamer solutions are known to exhibit thephenomenon of reverse thermal gelation thus remainingas solution at low temperature and gelling whentemperature increases. Furthermore, poloxamers werereported not to cause any damage on mucosalmembranes35, 36. Several attempts have been to modulatethe gelation temperature of poloxamer-based liquids.The gelation temperature of poloxamer solutions wasadjusted by modifying cross-linking agents andmonomers by mixing the different series of poloxamers,by changing the weight of poloxamers, or by changingthe pH and the ionic strength37, 38 . However, most

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previous studies have been focused on modulating onlythe gelation temperatures of poloxamer solutions. Therehas been a lack of knowledge on the strength and thebioadhesive force of gelled poloxamers, although thesetwo factors are crucial in designing desirable liquidsuppositories which do not leak out from the anus and donot reach the end of the colon after administration. KimCK et al., developed not only temperature-sensitive butalso mucoadhesive liquid suppositories containingacetaminophen using poloxamers and bioadhesivepolymers and investigated their effect on rectal mucouslining, gelation temperature, gel strength andbioadhesive forces1.

Bioadhesive PolymersBioadhesive polymers are generally hydrophilicmacromolecules that contain anionic charges and stronghydrogen bond forming groups (hydroxyl, oxide andcarboxyl groups) with high molecular weight, sufficientchain flexibility and surface energy properties favoringspreading onto mucus39. It includes synthetic polymerssuch as poly (acrylic acid) (PAA), hydroxypropylmethylcellulose and poly (methylacrylate) derivatives, aswell as naturally occurring polymers such as hyaluronicacid and chitosan40. Poly (acrylic acid) is considered as agood mucoadhesive but due to a high transitiontemperature and higher interfacial free energy, it cannotwet the mucosal surface to the optimal level which maylose interpenetration and inter diffusion of the polymer.These properties can be improved by copolymerizingwith polyethylene glycol (PEG) or poly (vinylpyrrolidone) (PVP). El- Leithy at al., prepared HPMCand carbopol 934 hydrogels containing diclofenacsodium chitosan microspheres for rectal administrationand they suggested microspheres allowed adhesion to therectal mucosa for subsequent controlled release behaviorwith no burst41.

Evaluation of SuppositoriesSolid suppositoriesAppearanceFor testing the appearance, randomly selectedsuppositories cut longitudinally and examine the surfaceswith naked eye42.

Weight variation testWeigh individually twenty suppositories and determinethe average weight. Compare the individual weights withthe average weight. No suppository should deviate fromaverage weight by more than 5% except two that maydeviate by not more than 10%43.

Liquefaction / softening timeFor determination of liquefaction / softening time, asimple apparatus can be fabricated in the laboratory44.Take a burette with broken stop-cock and cut suitably sothat it has a narrow opening on one side and broad

opening on another side. Dip the burette in hot watermaintained at 370 C so that narrow end faces towards hotwater. Introduce the sample suppository from the top ofthe burette through broad end and carefully push downits length until it reaches narrow end. Insert a glass rodweighing 30 g and 45 cm in length so that it rests overthe suppository. Record the time at which glass rodreaches the narrow end after complete melting ofsuppository represents the liquefaction time.

Micro-melting range testFor micro-melting range test, fill the formulation toabout 1 cm height in capillary tubes of 10 cm length anddip in a beaker containing water44. Raise the temperatureslowly and record temperature at which the massliquefies was recorded.

In vitro Dissolution StudiesIn vitro dissolution studies of suppositories are carriedout in USP XXIII tablet dissolution test apparatus(Electrolab TDT – 06N) employing a basket stirrer45. Aspecified volume of phosphate buffer pH 7.4 is used as adissolution medium maintained at 37±0.5º C.

Liquid suppositoriesGelation temperatureGelation temperature is determined by using the tubetilting method46. Transfer 2 ml aliquot of gel to test tubesimmersed in a water bath at 4°C and seal with aluminumfoil. Increase the temperature of water bath in incrementsof 1°C and allow to equilibrate for 5 min at each newsetting. Examine samples for gelation, which is said tohave occurred when the meniscus would no longer moveupon tilting through 90°C.

Measurement of gel strengthThe gel strength is determined according to the methodadopted by Kim et al. Put 50 g of liquid suppository in a100 ml graduated cylinder and gel in a thermostat at37°C. Place the apparatus for measuring the gel strength(weight 35 g) into the liquid suppository. Determine gelstrength by the time in seconds that apparatus take topenetrate 5 cm down through the gel.

Determination of the mucoadhesive forceThe mucoadhesive force, the detachment stress of theliquid suppositories is determined using a modificationof the mucoadhesive force-measuring device used byChoi et al. Cut a section from the fundus of rabbit rectumand secure instantly with the mucosal side out into eachglass vial. Store the vials at 36.5°C for 10 min. connectone vial to the balance and fix other with the poloxamergel added and adjust the height so that the gel is placedbetween the mucosal sides of both vials. Allow waterfrom a burette to fall in a beaker at a constant rate of 10mg/sec. Add increasing weight of water gradually thatwill detach the two vials. Determine mucoadhesive

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force, the detachment stress (dyne/cm²), from theminimal weights of water that detach 2 vials.

In-vivo tests experimentsMale Sprague–Dawley rats are used for in vivo studieshaving a weight of 250 ± 20 g. those rats are fasted for24–36 h prior to the experiments but allow free access towater9 . Divide fifteen rats into two groups. Use onegroup as control and administer 1.5 g liquidsuppositories containing drug/kg into the rectum 4 cmabove the anus through a stomach sonde needle. Blockthe entrance of the anus with a cyanoacrylate adhesive toprevent leakage of preparations from the anus during thepharmacokinetic experiment as it may lead to inaccuracyin pharmacokinetic data. Collect half milliliter of bloodfrom the right femoral artery at various intervals andcentrifuge at 3000 rpm for 10 min.

Mix plasma (0.05 ml) with 0.4 ml of acetonitrile solutioncontaining flufenamic acid (0.5_g/ml), as an internalstandard47. Centrifuge at 3000 rpm for 10 min toprecipitate the proteins. Evaporate the supernatant layer(0.4 ml) under N2 (g). Reconstitute the residue in 50µlof mobile phase and then analyze, the resulting solutionby HPLC equipped with an Inertsil ODS-3 C18 column(GL science, 0.5 µm, 15 cm × 0.46 cm i.d.) and UVdetector. The mobile phase should be acetoniltrile andphosphate buffer (pH 3.5) (4:6, volume ratio). Monitorthe eluent with a flow rate of 1.2 ml/min at a specifiedwavelength.

Kosior A prepared rectal suppositories withchorpropamide alone and chlorpropamide in thedispersion system with urea using a mixture of witepsolH15 and H19 and polyoxyethylene glycol as bases. Thedeveloped formulations were tested on the rabbits andcompared with the commercial tablets ofchlorpropamide48. Finally, he concluded that thesuppositories prepared with witepsol H15 along with thedispersed chlorpropamide caused much higher decreaseof blood glucose levels than the commercial tablets.

CONCLUSION:Rectal route is an effective alternative for oral drugadministration. Suppositories formulated by usingmucoadhsive polymers play a vital role in enhancing thebioavailability of drugs. An exhaustive study of solidand liquid suppository as a novel alternative for oraladministration reveals that suppositories are able toavoid the first pass effect and improve enzymatic drugstability as well as patient compliance. Narrowing theresearch on mucoadhesive polymers and suppositorybases would benefit the pharmaceutical science forexploring the alternative route of administration to oraladministration of drugs.

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