Suppositories, Inserts, and Sticks
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SUPPOSITORIES •
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Urethral administration of suppositories has become more acceptable with urethral suppositories in the treatment of male erectile dysfunction. In US less than 1% of drus are formulated as suppositories In !ermany hih as "% Proesterone #ainal inserts ha#e become much more widely used by post menopausal women
Employed for $ reasons 1. &. $.
Prom Promot ote e defe defeca cati tion on Intro Introdu duce ce dru drus s into into the the bod body y Treat reat anor anorect ectal al dise disease ases s
SUPPOSITOR9, I'SERT, -'* STI0: S;-PES •
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'ot often the (rst route of choice but a ood alternati#e when oral is inad#isable
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The downside downside of rectal rectal administration administration includes includes 1. &. $.
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Esthetics Esthetics and stima stima of #iola #iolatin tin the patien patient)s t)s dinity Poten Potentia tiall rect rectal al irri irritat tation ion *i+culty *i+culty in titratin titratin a corr correct ect dose due to limited strenths of commercial suppositories In treatin hospice patients, rectally administered medications are essential in palliati#e medicine -n ecellent dosae form for those patients to whom one does not want to administer numerous in/ections daily. 0an be administered to a#oid nausea and #omitin 0an often result in a fast onset of action
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*EI'ITIO'S •
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- suppository is a solid dosae form in which one or more -PIs are dispersed in a suitable base and molded or otherwise formed into a suitable shape for insertion into the rectum to pro#ide pro#ide local or systemic e2ect. -re intended for insertion into body ori(ces The deri#ation deri#ation of the word word suppository suppository is from from the latin 3supponere) 4 3to place under) as deri#ed from 3sub) 5under6 and ponere 5to place6 -n insert Is a solid dosae form that is inserted into a naturally occurrin 5non surical6 body ca#ity other than mouth or rectum, includin the #aina and urethra.
7edication stic8s are a con#enient form for administerin topical drus.
The shape and and si
ainal inserts 5suppositories or pessaries6 are usually lobular, o#iform, or cone=shaped and weih about " when cocoa butter is the base. Urethral inserts 5bouies6 are slender, pencil= shaped suppositories intended for insertion into the male or female urethra. 7ale urethral suppositories may be $ to ? mm in diameter and approimately 1@A mm lon. Bhen cocoa butter is employed as base, these suppositories weih about @. emale urethral suppositories are about half the lenth and weiht of the male urethral suppository, bein about CA mm lon and weihin about & when made of cocoa butter. 7edication stic8s are cylindrical in shape and enerally rane from " to &" . They are enerally pac8aed in an applicator tube for topical administration.
USES -'* -PPDI0-TIO'S •
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Suppositories containin drus such as aspirin, opiates for pain, erotamine tartrate for treatin miraine headaches are commonly used as suppositories. These drus drus are intended intended to be absorbed absorbed into the eneral circulation to pro#ide systemic dru e2ects. Eamples of suppositories i#en for systemic results = = =
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-minophylline 7orphine Prochlorpera
DO0-D -0TIO' •
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The ad#antaes of rectal administration include the followin 1. &.
-#oidin, at least partially, the (rst pass e2ect -#oidin the brea8down of certain drus that susceptible to astric deradation $. -bility to administer somewhat larer doses of drus @. -bility to administer drus that may ha#e an irritatin e2ect on the oral or astrointestinal mucosa ". -bility to administer unpleasant tastin or smellin drus ?. In children, the rectal route is especially useful. C. In patients eperiencin nausea and #omitin or when the patient is unconscious . The presence of disease of the upper astrointestinal tract that may interfere with dru absorption F. Ob/ectionable taste or odor of a dru 1A. -chie#ement of a rapid dru e2ect systematically •
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Pro#ides for a rapid and in many cases, etensi#e absorption of the acti#e inredient. RAPIDITY, INTENSITY AND DURATION are three parameters that must be considered durin formulation for rectal administration
The disad#antaes of suppositories and the reasons i#en for the infreGuent use of suppositories include the followin 1. &. $. @. ".
Dac8 of Heibility Epensi#e They ehibit #ariable e2ecti#eness 0annot be interchaned without ris8 of toicity 0an lea#e the anorectal site and ascend to the rectosimoid and descendin colon ?. *efecation may interrupt the absorption process of the dru C. -bsorbin surface area of the rectum is much smaller . The Huid content of the rectum is much less which may a2ect the dissolution rate F. Possibility of deradation of some drus 1A. The dose of a dru reGuired for rectal administration may be reater than or less than the dose of the same dru i#en orally 11. -natomic and physioloical factors and physicochemical factors of the dru and base
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These medicaments may be intended for retention within the ca#ity for local e2ects They may be intended to be absorbed for systemic e2ects Rectal suppositories intended for local action are most freGuently used to reli#e constipation -ntihemorrhoidal suppositories freGuent contain a number of components, includin local anesthetics, #asoconstrictors, astrinents, analesics, soothin emollients and protecti#e aents. !lycerin suppositories promote laation by local irritation of the mucous membranes >ainal suppositories or inserts intended for local e2ects are employed mainly as contracepti#es, as antiseptics, and as speci(c aents to combat in#adin pathoen
7ost commonly drus used •
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'onoynol F for contraception Trichomonacides to combat #ainitis -ntifunals, anti=infecti#esantibiotics
Urethal suppositories may be antibacterial or a local anesthetic preparati#e for a urethral eamination Stic8s are commonly used for local e2ectJ includes hydrationemollient, antibacterial, sunscreen, antipruritic
S9STE7I0 -0TIO' •
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or systemic e2ects, the mucous membranes of the rectum and #aina permit the absorption of many soluble drus Rectum is used freGuently as the site for the systemic absorption of drus
Eamples of drus administered rectally in the form of suppositories for their systemic e2ects include
Prochlorpera
P;9SIODO!I0-D -0TORS -'* *RU! EE0T
The physioloic factors that a2ect dru absorption from the rectum are 1. &. $. @.
Uretra! there are strati(ed columnar cells, then strati(ed sGuamous cells
0irculation route 0olonic contents p; Dac8 of bu2erin capacity
There are small mucus=secretin urethral lands that help protect the epithelium from the corrosi#e urine, The female urethra is supplied by blood #essels called the internal pudendal and #ainal arteries The male urethra is supplied by inferior #esical and middle rectal arteries The ner#e supply is #ia the pudendal ner#e
0IR0UD-TIO' ROUTE •
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The lower hemorrhoidal #eins surroundin the colon recei#e the absorbed dru and initiate its circulation Dymphatic circulation also assists in the absorption of rectally administered drus
p; -'* D-0: O LUERI'! 0 -P-0IT9 O T;E RE0T-D DUI*S •
The p; of the rectal Huid is enerally in the rane of C.& to C.@ and it has neliible bu2er capacity.
Rectal= the last few inches of the lare intestine constitute the rectum , terminatin at the anus Three types of hemorrhoidal #eins •
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Superior hemorrhoidal #ein 7iddle hemorrhoidal #ein Inferior hemorrhoidal #ein
-cts by transportin the acti#e principle absorbed in the rectum to the blood system The three hemorrhoidal #eins are lin8ed by an anastomosis networ8 -t least "A% to CA% of the acti#e inredients administered rectally ta8e the direct pathway
0ODO'I0 0O'TE'T •
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P;9SI0O0;E7I0-D -0TORS -'* *RU! EE0T •
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Epithelial tissue Doose connecti#e tissue 7uscle tissue . Lranches of the uterine arteries supply blood to the upper #aina The inferior #esicle arteries supply blood to the middle portion of the #aina The hemorrhoidal and internal pudendal arteries feed into the lower #aina The p; of the #aina is in the rane about @ to @." 'ormal #ainal dischare consists of about 1." of #ainal Huid daily
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Physicochemical factors include such properties as the relati#e solubility of the dru in lipid and in water and the particle si
DIPI*=B-TER SODULIDIT9
Vaginal – is a speciali
- dru will ob#iously ha#e reater opportunity to ma8e contact with the absorbin surface of the rectum and colon in the absence of fecal matter. -n e#acuant enema may be administered and allowed to act before the administration of a suppository of a dru to be absorbed.
The lipid=water partition coe+cient of a dru is an important consideration in the selection of the suppository base and in anticipatin dru release from the base - lipophilic dru that is distributed in a fatty suppository base in low concentration has less tendency to escape to the surroundin aGueous Huids than a hydrophilic substance in a fatty base.
Eample of water=soluble bases
Polyethylene lycols= that dissol#e In anorectal Huids
P-RTI0DE SIME •
The smaller the particle, the reater the surface area and the reater the chance for rapid absorption.
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The rate of absorption is inHuenced by the solubili
-TT9 OR ODE-!I'OUS L-SES •
SUPPOSITOR9 L-SES •
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Suppository bases play an important role in the release of the medication they hold and therefore, in the a#ailability of the dru. It should remain solid at room temperature but soften, melt, or dissol#e readily at body temperature 0ocoa butter melts Guic8ly at body temperature !lycerinated elatin or polyethylene lycol, both of which dissol#e slowly in body Huids. Treatment of anorectal disorders, cocoa butter appears to be the superior base
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The absence of any dru interaction between the two aents should be ascertained before or durin formulation. 7orphine sulfate in slow=release suppositories is prepare in a base that includes a material such as alinic acid, which will prolon the release of the dru o#er se#eral hours
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0D-SSII0-TIO' O L-SES 1. &. $.
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atty or oleainous bases Bater=soluble or water miscible bases 7iscellaneous bases= enerally combination of lipophilic and hydrophilic substances - suppository base should be physically and chemically stable, non=irritatin, non=toic , non=sensiti
*rus that lower the meltin point of the base
0amphor 0hloral hydrate 7entol Phenool Thymol
atty bases are perhaps the most freGuently employed suppository bases, principally because cocoa butter is a member of this substances.
-mon the other fatty or oleainous materials used in suppository bases
'-TURE O T;E L-SE •
>olatile oils
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;ydroenated fatty acids of #eetable oils such as palm 8ernel oil, and cottonseed oil at=based compounds containin compounds of lycerin such as palmitic and stearic acid 5lyceryl monostearate and lyceryl monopalmitate6
Some bases are prepared with the fatty materials emulsi(ed or with an emulsifyin aent present to prompt emulsi(cation when the suppository ma8es contact with the aGueous body Huids. 0ocoa Lutter, ', is the fat obtained from the roasted seed of Theobroma cacao. It is a yellowish=white solid. It is a trilyceride 0ocoa butter melts N $A0 to $?0. It is an ideal suppository base 0ocoa butter ehibits mar8ed polumorphism or eistence in se#eral crystalline forms Substances such as phenol and chloralhydrate ha#e a tendency to lower the meltin point of cocoa butter. Solidifyin aents li8e cetyl esters was or beeswa may be melted with the cocoa butter to compensate for the softenin e2ect of the added substance
Other bases 1. &.
attibase 4 trilycerides from palm, palm 8ernel, and coconut oils Becobee bases 4 trilycerides of saturated fatty acids
B-TER=SODULDE -'* B-TER=7IS0ILDE L-SES •
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The main members of this roup are lycerinated elatin and polyethylene lycols - lycerinated elatin base is most freGuently used in the preparation of #ainal suppositories The lycerinated elatin base is slower to soften and mi with the physioloic Huids than is cocoa butter and therefore pro#ides a slower release !lycerinated elatin base suppositories ha#e a tendency to absorb moisture
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They must be protected from atmospheric moisture The suppository may ha#e a dehydratin e2ect and irritate tissues upon insertion Urethral suppositories may be prepared from a lycerinated elatin base Urethral suppositories of lycerinated elatin are much more easily inserted Polyethylene lycols are polymers of ethylene oide and water prepared to #arious chain lenths, molecular weihts and physical states The numeric desinations refer to the a#erae molecular weiht of each of the polymers. Polyethylene lycols ha#in a#erae molecular weihts of reater than 1,AAA are wa=li8e white solids whose hardness increases Proesterone #ainal suppositories are used in pre=menstrual syndrome. They are commonly molded with either a polyethylene lycol base or a fatty acid base Polyethylene lycol suppositories do not melt at body temperature but rather dissol#e slowly in the body)s Huids Polyethylene lycol=based suppositories do not lea8 from the ori(ce Poloamers are water=soluble bloc8 copolymers with a wide rane of uses Oluronics D@@, D?&, D?@ amd ? are potential suppository bases The poloamers ha#e practically no odor or taste
OR7UD-TIO' >-RI-LDES ormulation #ariables that are enerally considered include
The nature and form of the acti#e principle The physical state, particle dimensions and the speci(c surface of product The solubility of the dru in #arious bases The presence or absence of ad/u#ants The nature and type of dosae form in which the acti#e principle is incorporated Pharmaceutical procedures used in the preparation of the dosae form
P;9SI0-D ST-TE •
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-n acti#e dru can be a solid, liGuid, or semi= solid in nature or solids, the dru)s particle si
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It is necessary to ta8e up the liGuid into the suppository base usin one of se#eral techiniGues such as formin emulsion,etc or the semisolids or paste=type drus, it can be either mied with a solid that will ser#e to thic8en the dru.
P-RTI0DE SIME •
If a dru is readily soluble, the inHuence of particle si
SODULIDIT9 •
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Increased solubility of the acti#e in the base can impro#e product homoeneity It may also delay the release of the acti#e if there is too reat an a+nity f the dru for the suppository #ehicle.
>IS0OSIT9 •
If the #iscosity of a base is low, it may be necessary to add suspendin aent such as silica el
LRITTDE'ESS •
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0ocoa butter suppositories are usually not brittle unless the percentae of solids present is hih Synthetic fat bases with hih stearate concentrations or those that are hihly hydroenated are typically more brittle
>ODU7E 0O'TR-0TIO' •
Lases, ecepients and acti#e inredients enerally occupy less space at lower temperatures than at hiher temperatures
SPE0I-D PROLDE7S •
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;ard, crystalline materials can be incorporated either by pul#eri
- number of inredients are incompatible with PE! bases includin
Len
-spirin Sil#er salts Tannic acid
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Other materials reported to ha#e a tendency to crystalli
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Sodium barbital Salicylic ac#id 0amphor
Polyethylene lycol=based suppositories may be irritatin to some patients Trilyceride=type bases can sometimes accept up to about "A% lycerin without much di+culty
PREP-R-TIO' O SUPPOSITORIES
P-0:-!I'! -'* STOR-!E •
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Suppositories are prepared by two methods •
-. 7oldin from a melt L. ;and rollin and shapin
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SUPPOSITOR9 7OD*S • •
7olds in common use today are made from stainless steel, aluminum, brass or plastic
DULRI0-TIO' O T;E 7OD* •
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Dubrication is seldom necessary when the base is cocoa butter or polyethylene lycol Dubrication is usually necessary with lycerinated elatin
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In (llin each suppository ca#ity, the pourin must be continuous to pre#ent layerin
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;-'* RODDI'! -'* S;-PI'! •
;and rollin and shapin is a historic part of the art of the pharmacist
Physical obser#ation can enerally detect physical stability problems includin softenin, hardenin, dryin, crac8in, separation, polymorphs
0;E7I0-D ST-LIDI9 •
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!lycerin suppositories and lycerinated elatin suppositories are pac8aed in tihtly closed lass containers to pre#ent a chane in moisture content Suppositories prepared form cocoa butter base are usually indi#idually wrapped or otherwise separated in compartmented boes to pre#ent contact and adhesion Suppositories containin liht=sensiti#e drus are indi#idually wrapped in an opaGue material such as metallic foil 7ost commercial suppositories are indi#idually wrapped in either foil or plastic Some are pac8aed in a continuous strip Suppositories are commonly pac8aed in slide boes or in plastic boes It is necessary to maintain them in a cool palce Suppositories made from a base of polyethylene lycol may be stored at usual room temperatures Suppositories stored in hih humidity mas absorb moisture
P;9SI0-D ST-LIDIT9
PREP-RI'! -'* POURI'! T;E 7EDT •
uality control procedures listed in the USP $?= ' $1 for manufactured suppositories and inserts include identi(cation, assay, and in some cases, loss on dryin, disinteration and dissolution
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In wor8in with suppositories, the ma/ority will be anhydrous Bater may be present to help incorporate the dru into base It may be present as part of the hydrated form of the dru components) crystalline structure If emulsions or suspensions are incorporated into suppositories, water may be present
7-'U-0TURI'! SUPPOSITORIES •
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7anufactured suppositories are enerally prepared by the melt fusion method The process starts with two main components the pac8ain shell material and the molten bul8 product
U-DIT9 0O'TROD
LE99O'*=USE *-TI'! OR 0O7PU'*E* SUPPOSITORIES •
The completed compounded suppositories are enerally considered dry or non=aGueous
EQPIR-TIO' *-TI'! OR 7-'U-0TURE* SUPPOSITORIES Eempt from this reGuirement are
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;omeopathic dru products -llerenic etracts In#estiational new drus
Ecessi#e softenin is the ma/or indication of instability in suppositories -s a eneral rule, suppositories should be stored in a refrierator
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0O7POU'*I'! URET;R-D SUPPOSITORIES •
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I'OR7I'! -'* E*U0-TI'! T;E P-TIE'T •
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The pharmacist is obliated to inform the patient about the proper storae conditions for both prescription and non prescription products and to suest a reasonable estimate of the time after which the medication should be discarded. Patients should be encouraed to clean out their dru storae cabinets periodically
RE0T-D SUPPOSITORIES Intended to be absorbed into the eneral curcylation to pro#ide systemic e2ects
- much smaller urethral suppository has been introduced for the administration of alprostadil in the treatment of erectile dysfunction
- straw or thin lass tube can be used as the mold when preparin urethral suppositories The 7USE 5aprostadil6 urethral micro= suppository 5>i#us inc.6 is a sinle=used medicated transurethral system for the deli#ery of alprostadil in the male urethra
>-!I'-D I'SERTS •
These preparations are employed principally to combat infections in the female enitor urinary tract, to restore the #ainal mucosa to its normal state, and for contraception.
-mon the anti=infecti#e aents in commercial #ainal preparations are
-spirin i#en for pain Erotamine tartrate for treatin miraine headaches Theophylline as a smooth muscle relaant in treatin asthma 0hlorptoma
-nti=funals
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Suppositories are also intended to pro#ide local action within the perianal area Docal anesthetic suppositories are commonly employed to relie#e pruritus ani 0athartic suppositories are contact=type aents that act directly on the colonic mucosa to produce normal peristalsis 0athartic suppositories are more rapid actin than orally administered medication !lycerin, a hyroscopic material, contributes to the laati#e e2ect of the suppository
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URET;R-D SUPPOSITORIES
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Suppositories for urethra administration tend to be thinner and tapered, often about "mm in diameter They ha#e been used for the treatment of local infections
Triple sulfas Sulfanilamide Po#idone Iodine 0lindamycin phosphate 7etronida
>-!I'-D I'SERTS 5T-LDETS6
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'ystatin 0lotrima
>ainal inserts 5tablets5 are widely used today as they are easy to manufacture, more stable and less messy -ccompanied in their pac8ain with a plastic inserter, a de#ice for easy placement of the tablet within the #aina They are prepared by tablet compression and are commonly formulated to contain lactose as the base or (ller, a disinteratin aent such as starch, a dispersin aent such as poly#inylpyrrolidone, and a table lubricant such a manesium stearate
7E*I0-TIO' STI0:S •
The medication stic8, a fairly recent preparation, is used for both cosmetic and medical purposes
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7edication stic8s are prepared similar to suppositories ecept that the melt Is poured into the administerin de#ice or tube
0DI'I0-D 0O'SI*ER-TIO'S •
7eltin bases •
0ocoa butter Petrolatum waes Polyethylene lycols 5PE!S6
Penetration enhancers !lycerin Propylene lycol -lcohol Surfactants . Usin waes, oils, or plain polymers suchs as PE!s alone achie#es a topical e2ect
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Rub cocoa butter suppositories ently with (ners to melt the surface to pro#ide lubrication for insertion !lycerinated elatin or polyethylene lycol suppositories should be moistened with water to enhance lubrication The shape of the suppository determines how it will be inserted. Lullet=shaped rectal suppositories should be inserted point=end (rst
