Quality control of suppositories

1 Royal Pharmaceutical Society of Great BritainSeptember 16, 2007 23:309 Quality control of suppositoriesQUALITY control procedures listed in the USPharmacopeia (USP30-NF25) for manufacturedsuppositories include identification, assay, and,in some cases, water content, residual solvent,dissolution, and content uniformity: Identification: Identification tests are com-monly used for the identification and confirma-tion of official articles. Assay: Assay and test procedures are used todetermine compliance with the pharmacopeialstandards of identity, strength, Quality , and pu-rity. Chromatographic methods are commonlyused for detection and quantitation. Dissolution: Dissolution testing is used to de-termine compliance with the dissolution require-ments, if present in the individual test measures the rate and extent of a drugdissolving in a defined medium under definedconditions. Water: As many pharmacopeial articles eitherare hydrates or contain water in adsorbed form,the determination of water content may be im-portant in demonstrating compliance with Phar-macopeial standards.

2 Three methods are com-monly used: Method I is a titrimetric method,Method II is an azeotropic method, and MethodIII is a gravimetric method. Content uniformity: Content uniformity is re-quired in some monographs to ensure the consis-tency of dosage units. These dosage units shouldhave a drug substance content within a narrowrange around the label claim. Weight variationand content uniformity testing involving groupsand individual dosage units are used. Residual solvents: For pharmacopeial purposes,these are defined as organic volatile chemicalsthat are used or produced in the manufacture ofdrug substances or excipients, or in the prepara-tion of drug products. They are not completely re-moved during processing but should be removedto the extent that is possible and considerations in dispensing practicefor suppositories also include observations onexcessive softening and oil stains on suppositories can be checked forcalculations of theoretical and actual weight andweight variation, color, hardness, surface texture,and overall Quality control includes physi-cal and chemical aspects of the product ( ).

3 Physical analysis includes visual examina-tion (physical appearance), uniformity of weight,uniformity of texture, melting point, liquefac-tion time, melting and solidification time, andmechanical strength. Chemical testing includesanalysis of the activity and dissolution uniformity of texture can be assessed bysectioning a suppository longitudinally and lat-erally, and ensuring that each section presents asmooth, uniform list of official USP suppositories and requiredquality tests is given in Table analysisVisual examinationColor and the surface characteristics of the sup-pository are relatively easy to assess. It is impor-tant to check for the absence of fissuring, pitting,fat blooming, exudation, sedimentation, and themigration of the active ingredients. Suppositoriescan be observed as an intact unit and also bysplitting them Pharmaceutical Society of Great BritainSeptember 16, 2007 23:30140 SuppositoriesBox standard operating procedure: performing physical Quality assessment of The purpose of this procedure is toprovide a method of documenting uniformity betweenbatches and physical Quality assessment tests of andobservations on , balance, graduates, beaker, Conduct the appropriate tests andrecord the results/observations on the Physical QualityAssessment Form for suppositories (Box ).

4 Accurately weigh the product on gravity To calculate the specific gravity,one must know the weight and volume of the the weight of the individual dosage form ora strip/package of the dosage forms (tared weight).To determine the volume of water displaced, do thefollowing:Single unit:1 Place mL of water in a 10 mL the dosage form and read the water mL from the level in step 2 to determinethe volume of water occupied by the dosage the dosage form floats, place a weight attachedto a paper clip in the graduate prior to adding thewater to the mL mark. Then, wrap one end of thepaper clip around the dosage form to hold it below thewater surface and place it in the graduate. Proceed as instep unit packages (suppository strip):1 Place the empty package in a beaker that will holdit with minimal extra an exact known quantity of water to cover theproduct. It may be necessary to add a weight to thepackage; this same weight should be used for the a fine-line marker and with the beaker settingon a level surface, mark the water level on the outsideof the the beaker contents, empty and dry the dosage form (and the weight if used) intothe the same volume of water as in step 2 intoa the water into the beaker only to the markfrom step 3.

5 (Note: Do quickly before the dosage formdissolves.)8 Measure the volume of water remaining in :Now that the weight and volume of the productare obtained, the specific gravity can be cal-culated by dividing the weight (grams) by thevolume (in milliliters). drug assay results As appropriate, haverepresentative samples of the product assayed foractive drug content by a contract analytical can be assessed by storing the product at room,refrigerated and/or frozen temperatures and having theassay repeated on the stored of product It may be advisable to use a colorchart for determining the actual color of the clarity by visual of surface Observe the product to deter-mine smoothness of the (dry, oily/moist) Determine whetherthe product appears dry or (tacky, plastic, elastic) Touch the product todetermine whether it is sticky (tacky) or hard (plastic) orbounces back (elastic).

6 Test (for fatty acid, cocoa butter and oil-based products):Royal Pharmaceutical Society of Great BritainSeptember 16, 2007 23:30 Chapter 9 Quality control of suppositories141 Box a 200 mL beaker of water to 37 Conamagnetic stirring unit set at about 50 a dosage unit to the 30 minutes, record your observations as yes,no or partially melts on the scale : It may be necessary to add a weight to thesedosage units to pull them below the water test (for polyethylene glycol, gelatin andwater-soluble products):1 Proceed as in the melting 30 minutes, record your observations as yes,no or partially dissolved on the scale observation Describe the appearanceand organoleptic qualities of the stability Prepare a few additional dosageforms, package and label ( For physical stability ob-servations ). Weekly, observe the product for signs ofdiscoloration, dryness, cracking, mottling, mold growth,etc.

7 Record a descriptive observation on the form ateach observation interval. There are sufficient lines forobservations for eight weeks (approximately 60 days).ShapeIt is advisable to check the shape of the sup-pository to see if it is consistent, irrespectiveof whether the suppository is ogive or conditionThe following can be checked: brilliance, dull-ness, mottling, cracks, dark regions, axial cavities,bursts, air bubbles, holes, intensity, nature and homogeneity of thecolor should be of odor can prevent confusion whensimilar suppositories are being processed. Achange in the odor may also be indicative of adegradation can be weighed on an automaticbalance, obtaining the weight of 10 the weight is found to be too small, it is advis-able to check whether the mold is being well filledand whether there are axial cavities or air bubblescaused by badly adjusted mechanical stirring orthe presence of an undesirable surfactant.

8 It isalso important to check that the batch of suppos-itories is homogeneous. If the weight is foundto be too high, check that scraping has beencarried out correctly, and also that the mixtureis homogeneous. Lastly, the weight may decreaseduring aging when the suppositories containvolatile substances, especially if the packaging isnot range (melting point, melting zone)Melting range or melting zone is the term oftenpreferred by some rather than melting suppository bases and medicated suppos-itories are mixtures, and so do not have a precisemelting point. Routinely, though, we continueto call the physical phenomenon obtained underrigorous conditions the melting release rate of the suppository is relatedto its melting point; it is therefore critical thatthis test be evaluated using a non-destructivemethod. A number of different techniques areused to study melting behavior, including theopen capillary tube, the U-tube, and the droppoint methods (Figures , , and ).

9 OneRoyal Pharmaceutical Society of Great BritainSeptember 16, 2007 23:30142 SuppositoriesBox Quality assessment form for compounded suppositoriesProduct:Date:Lot/Rx number:Form: SuppositoryCharacteristicTheoreticalActu alNormal RangeWeight/volumeSpecific gravityActive drug assay resultsInitial assayAfter storage No. 1 After storage No. 2 ColorofproductClarityClear12345 OpaqueTexture-surfaceSmooth12345 RoughAppears dryYes12345 NoAppearanceDry12345 Oily/moistFeels tackyYes12345 NoFeels plasticYes12345 NoFeels elasticYes12345 NoMelting testYes12345 NoDissolution testYes12345 NoSample set aside for physical observation:YesNoIf yes, results:DateObservationshortcoming is the use of limited data to de-scribe a continuous, complex melting processoccurring in successive steps involving multiplecomponents, including various molecular weighttriglycerides, polymers, or other methods used are similar in principlebut include different steps and techniques.

10 Ingeneral they include the set-up of the equipment,placement of the suppository dosage unit in theapparatus, followed by the application of heatand observation for a change in the system, suchas melting or movement. The results obtainedusing different methods do not always agree, soit is important to use a consistent general, the melting point should be equalto or less than 37 C. A non- destructive methodmust be used because if the suppository is meltedbefore a measurement is made, the supposi-tory constituents may be transformed into ametastable melting test consists of placing a suppos-itory on the surface of water thermostaticallycontrolled at 37 C and verifying the completemelting of the suppository in a few minutes. point determinationThe use of a U-shaped capillary tube to determinemelting point provides precise information forexcipient control and consistency in productionRoyal Pharmaceutical Society of Great BritainSeptember 16, 2007 23:30 Chapter 9 Quality control of suppositories143 Table USP suppositories and required Quality testingMonographIdentificationAssayDisso lutionWaterContentuniformityResidualsolv entsAcetaminophenxx xAminophyllineaxx Aspirinbxx Bisacodylxx Chlorpromazinecxx Ergotamine tartrate and caffeinexx xGlycerinxx x xIndometacinxxx xxMiconazole nitratexx xMorphine sulfate x xxNystatin x x Oxymorphone hydrochloridexx xProchlorperazinexx Progesterone x xxPromethazine hydrochloridexx Thiethylperazine maleatexx xaEthylenediamine content of free salicylic acid alkylated phenothiazines those suppositories containing soluble activeprinciples.