Plan 1.Rectal preparations. Classification of the rectal preparations. 2. Suppositories. General characteristic of suppositories. 3. Methods of suppositories production in industrial. 4. Equipments for suppositories production in industrial. 5. Standardizationof suppositories.
Rectal preparations are intended for rectal use in order toobtain a systemic or local effect, or they may be intendedfor diagnosticpurposes. Where applicable, containers for rectalpreparationscomply with the requirements for Materials used for themanufacture of containers andContainers.
Several categories of rectal preparations: • suppositories, • rectal capsules, • rectal solutions, emulsions and suspensions, • powders and tablets for rectal solutions and suspensions, • semi-solid rectal preparations, • rectal foams, • rectal tampons.
Suppositories – dosage form which are solid at room temperature and melting or dissolving at body temperature are intended for administration in the body cavity. Suppositories are solid, single-dose preparations. The shape, volume and consistency of suppositories are suitable for rectal administration.
Rectal capsules (shell suppositories) are solid, single-dosepreparations generally similar to soft capsules as defined inthe monograph on Capsules except that they mayhave lubricating coatings. They are ofelongated shape, aresmooth and have a uniform externalappearance.
Rectal solutions, emulsions andsuspensions are liquidpreparationsintended for rectal use in order to obtaina systemic or local effect, or they may beintended fordiagnostic purposes. Rectal solutions, emulsions and suspensions are supplied in single-dose containers and they contain one or more active substances dissolved or dispersed in water, glycerol or macrogols or other suitable solvents. Emulsions may show evidence of phase separation but are readily redispersed on shaking. Suspensions may show a sediment which is readily dispersible on shaking to give a suspension which remains sufficiently stable to enable the correct dose to be delivered.
Rectal tampons are solid, single-dose preparations intended to be inserted into the lower part of the rectum for a limited time.
Suppositories contain one or more active substances dispersed or dissolved in a suitable basis which may be soluble or dispersible in water or may melt at body temperature. Excipients such as • diluents, • adsorbents, • surface-active agents, • lubricants, • antimicrobial preservatives • colouring matter authorised by the competent authority, may be added if necessary.
Classification • Rectal suppositories for adults weigh 2 gm and are torpedo shape. Children's suppositories weigh about 1 gm. • Vaginal suppositories or Pessaries weigh about 3-5gm and are moulded in globular or oviform shape or compressed on a tablet press into conical shapes. • Urethral suppositories called bogies are pencil shape. Those intended for males weigh 4 gm each and are 100-150 mm long while those for females are 2 gm each and 60-75 mm in length.
Advantages of suppositories: 1. Suppositories are precise dosage forms containing accurate quantities of medicament(s). 2. Suppositories have been used for systemic distribution when the oral administration was not suitable, as in unconscious patients and infants. Suppositories simplify or eliminate the problem of infant medication. 3. Suppositories allow administration of some medicaments, which are not tolerated orally, e.g. medicaments which are sensitive to the gastric pH and gastric enzymes.
Advantages of suppositories: 4. Suppositories permit administration of medicament that interrupt the functionality of the gastrointestinal tract e.g. drugs irritating to the stomach. 5. Suppositories are useful when the stomach is not the ideal position to receive medication such as in case of nausea and vomiting. 6. Suppositories are suitable when local effect is wanted as in the treatment of rectal, vaginal and urethral diseases. 7. Suppositories have shown faster onset of action than found after oral administration as the drug is directly absorbed from the mucosa into the venous circulation.
Advantages of suppositories: 8. Drugs destroyed by portal circulation may bypass the liver circulation, where many drugs subject to metabolic changes (first pass effect).
Disadvantages of Suppositories: • The problem of patient acceptability. • Suppositories are not suitable for patients suffering from diarrhea. • In some cases the total amount of the drug must be given will be either too irritating or in greater amount than reasonably can be placed into suppository. • Incomplete absorption may be obtained because suppository usually promotes evacuation of the bowel.
On the speed of absorption of drugs with suppositories such physiological factors affect: • State of the rectum. • Circulation of blood suction surface. • Muscle tone and mucus layer on the surface of the walls of the rectum. • - Nature of the basis is the most influential factor on the absorption of active ingredients from suppositories.
Methods of suppositories production in industrial 1. Fusion Moulding 2. Compression Moulding Hands moulding is used only in the pharmacy!
Method Fusion Moulding It involves first melting the suppository base, and then dispersing or dissolving the drug in the melted base. The mixture is poured into a suppository mold. When the mixture has congealed, the suppositories are removed from the mold. The fusion method can be used with all types of suppositories and must be used with most of them.
Technological stages of industrial production of suppositories by fusion moulding 1) Production of bases; 2) Preparation of drugs and obtaining concentrate; 3) Introduction drugs in the base; 4) Formation (and packing) suppositories; 5) Packing of suppositories.
Stage of production bases: 1. Weighing components of the base. 2. In stainless steel reactor with a steam jacket and stirrer components of base are alloyed at 60-70°C and stirring for 40 minutes. 3. The base is filtered through a druc-filter, using brass mesh or belting, and analyzed by point of the melting, solidification and times of total deformation. 4. Then it is transferred to the hardware department.
Preparation of drugs and obtaining concentrate 1. Making of the solution or suspension of medicines: - Water-soluble components are dissolved in water, heated to 45 °C, - Fat soluble components are dissolved in part of the molted fat base. - Substances insoluble in water and base, are used as suspension: Pre-crushed medicines are mixed in a reactor with an equal number of base (or one and half), heated to temperature of 40-50 °C.
Preparation of drugs and obtaining concentrate 2. The obtained concentrate is cooled and grinded by colloid miller or for thermo sensitive substances - by three rolls ointment rubber. Furthermore, for obtaining of high quality suspensions rotary-pulsation apparatus, rotary-screw pumps and other equipment can be used. 3. These concentrates are filtered through calico, and then mixed with the the base.
Introduction medicines in the bases Concentrate is poured by the pump (through a hose caprone sieve) into reactor (with an anchor stirrer or turbine) for mixing with the base.
Stage of formation and packing suppositories: Lines such as «Sarong 200 S» with direct dosing of formed mass in the cells are formed of polyvinylchloride films is used for fesion suppositories with followed styling of products in bundles.
Stage of formation suppositories: 1. From the two vertical set rolls aluminium foil tapes or polyvinylchloride films are served. 2. Then both tapes are formed in bowl-like halves, which are connected in to the complete form and heat-sealed at the temperature. At the top of each form hole remains open for filling by a needle for filling, which pours on molten suppository mass. Thus, a formed from foil packaging is simultaneously used by fusion moulds. 3. On the next position packaging is hermetically sealed.
From the two vertical set rolls aluminium foil tapes or polyvinylchloride films are served.
Disadvantage of the fusion method: 1. It's possible a bundle of suppository mass into separate layers during the measuring and harden especially in cases of the insoluble ingredients with a large density or fluid that are not mixed with water present. 2. This method is not suitable for thermo sensitive substances.
To prevent bundle of suppository mass: 1. You must to increase the viscosity of the base. 2. Avoid high temperature at the fusion of the mass. 3. Carry out mixing of the mass before fusion in the mould.
The method of compressing is non-thermal method of suppositories producing by compressing of cooled mass and crushed the mix of the base and drugs.
The advantages of compressing method: 1. Is the ability to prevent the destruction of thermostable drugs, lack of sedimentation of the active ingredient and avoid possible incompatibility with the molten suppository base. This method is applicable when using plastic bases. 2. In production of pressed suppositories do not need to exert considerable efforts to eject because the fat particles act as an effective base oils in the wall layer as a result of severe plastic leakage. .
The advantages of compressing method: Compressing method is particularly suitable in the production of suppositories with cardiac glycosides, some thermosensitive hormones, biogenic stimulators, because the production process to yield high precision dosing, thermal stability of drugs/
Standardization of suppositories 1. Description 2. Identification and quantitative determination of active substances and antimicrobial preservatives 3. Average mass and uniformity of mass 4. Disintegration 5. Uniformity of content 6. Melting point or a full strain 7. Dissolution 8. Impurities 9. Microbiological purity 10. If necessary, additional control acid and peroxide numbers 11. Particle size
Directions of suppositories improving : 1.Lyophilized suppositories 2. Porous suppositories 3. Multilayered suppositories 4. Suppositories with film-coated 5. Painted suppositories