实验7栓剂的制备讲稿_工业药剂学

2020-03-01 19:44:02 来源：范文大全收藏下载本文

Experiment 7 Preparation of suppositories

Purposes

1.To know the characters and applications of the bases of suppositories.

2.To master the characters and applications of fusion method to prepare suppositories.

Introduction Suppositories are preparations made by incorporating medicaments in suitable bases, intended for rectal administration.Suppositories are made in different shapes and sizes according to the site of action and their function, generally include vaginal suppository and rectal suppository.

The drug and bases in suppositories should be thoroughly mixed.The suppositories are smooth and uniform in appearance.Suppositories are nonirritating and melting, softening or diolving when inserted in the rectum and are miscible with body fluid to release the medicaments gradually thus exert local or systemic effects.Suppositories are sufficiently hard to withstand handling or packaging without deformation

Cocoa butter, glycerinated gelatin, hydrogenated vegetable oils and mixtures of polyethylene glycol may be used as suppository bases.The suppository base employed has a marked influence on the release of the active ingredient incorporated in it.While cocoa butter melts quickly at body temperature, it is immiscible with body fluids and this inhibits the diffusion of fat-soluble drugs to the affected sites.Polyethylene glycol is a suitable base for some antiseptics.In cases where systemic action is expected, it is preferable to incorporate the ionized rather than the nonionized form of the drug, in order to maximize bioavailability.Although un-ionized drugs partition more readily out of water-miscible bases such as glycerinated gelatin and polyethylene glycol, the bases themselves tend to diolve very slowly and thus retard release in this manner.Oleaginous vehicles such as cocoa butter are seldom used in vaginal preparations because of the nonabsorbable residue formed, while glycerinated gelatin is seldom used in recta because of its slow diolution.Cocoa butter and its substitutes (Hard Fat) are superior for allaying irritation.As in preparations intended for treating internal hemorrhoids.General the volume of mold of suppositories are fixed, but different suppositories may have different weight as the density of the drugs and bases are different.The weight of the suppository bases can be determined by calculating the displacement value, which is definite as the weight proportion of drug to cocoa butter with the same volume.For example, the displacement value of tannic acid is 1.6, which means the volume of 1.6g tannic acids is equivalent to that of 1g cocoa butters.Generally the bases of suppository include greasy bases and water-soluble bases.It can be prepared by the fusion method. Equipments and Materials 1.Equipments

mold of vaginal suppository, mold of rectal suppository, evaporating dish, water bath, ice bath, electric stove, analytical balance, disintegration determination apparatus, etc.2.Materials

cocoa butter, glycerol, gelatin, stearic acid, sodium carbonate, sodium bicarbonate, tannic acid, chlorhexide acetate, borneol, citric acid, liquid paraffin, ethanol, tween 80, distilled water PEG400, PEG6000, etc.

Procedures 1.Glycerol suppository (1) Formulation Glycerol Sodium carbonate Stearic Acid Distilled water (2) Preparation Sodium carbonate, distilled water and glycerol is mixed in the evaporating dish above the water bath.Add stearic acid slowly into this evaporating dish in the agitation.Then pour this solution into the molds of rectal suppository smeared with liquid paraffin when the mixture turns into settled solution.After they are cooled, scrape off the unneceary parts, and the final products can be got.2.Tannic acid suppository (1) Formulation

Amount per piece, gram

Total amount per 4 pieces, gram

Tannic acid

0.2g

0.8g Cocoa butter

Q.S

Q.S (2) Preparation

① Determination the weight of the blank suppository Add 4g cocoa butter into evaporating dish which is above the water bath, take away the water bath immediately when the second three parts of the cocoa butter have been melted, keep stirring until all the cocoa butter has been melted.Pour this solution into the molds of rectal suppository smeared with lubricant.After they are cooled, scrape off the unneceary parts, and the final products can be got.Weigh the total weight and calculate the average that is the amount of black suppositories.② Calculate the amount of cocoa butter in one piece of suppository according to the displacement value of drugs.Displacement value (DV) of tannic acid is 1.6, the weight of blank suppositories determined

8g 0.2g 0.8g 1g is x, if three pieces of suppositories are need to be prepared, the real amount is calculated as four pieces.So the amount (g) of cocoa butter is

4x0.24.1.6③ Calculate the amount of cocoa butter by the method of step (1) and add it to the evaporating dish, keep heating in the water bath until the cocoa butter close to melt.Take away the evaporating dish, and add the tannic acid, stir the mixture fully.Pour this mixture into the molds of rectal suppository smeared with lubricant when it close to congeal and cool in the ice bath immediately, scrape off the unneceary part, and the final products can be got.*Purpose: The above two formulations are treated to haemorrhoids. 3.Chlorhexidini Acetas suppository (1) Formulation Chlorhexide Acetate Tween 80 Borneol Ethanol Glycerol Gelatin (minute grain) Distilled water Total sum: two pieces (2) Preparation Add the gelatin of the formulation in evaporating dish and swell in 20ml of distilled water for 30min to make it soft.Add glycerol, and heat the mixture in water bath to make gelatin diolve, keep heating until the weight of mixture is 18-20g.Diolve chlorhexide acetate in tween 80 and borneol in ethanol respectively, mix the above two solutions and add the gelatin solution prepared in the agitation.Pour this mixture into the molds of vaginal suppository smeared with liquid paraffin immediately.After they are cooled, scrape off the unneceary parts.The final products can be got.

4.Tinidazole effervescent suppository (1) Formulation

Amount per piece,g Tinidazole PEG 400 PEG 6000 Sodium bicarbonate Acid citric (2) Preparation Sodium bicarbonate and acid citric must be grinded to fine powder.PEG 400 and PEG 6000

0.25g 1.15g 0.50g 0.28g 0.26g 0.05g 0.2g 0.01g 0.5mL 9.0g 2.7g

Add up to 20.0g are mixed and melted in the water bath.Then add tinidazole, sodium bicarbonate and acid citric into the liquid in the agitation and mix completely, pour this mixture into the molds of rectal suppository immediately.After they are cooled, scrape off the unneceary parts.Then the final products can be got.*Purpose: The above two formulations are treated to vaginal inflammations.5.Evaluation or Determination of suppository (1) Weight variation Weigh accurately 10 suppositories and calculate the average weight, then weigh individually each of the 10 suppositories.Not more than one of the individual weight deviates from the average weight by more than the weight variation limit, and none deviates by more than twice of that percentage.The weight variation limit of suppositories is shown as following: weight variation ≤±10% if the average weight of suppository ≤1.0g, weight variation ≤±7.5% if the average weight of suppository is 1.0-3.0g and weight variation ≤±5% if the average weight of suppository is ＞3.0g.The weight variation of suppositories must comply with the above requirements.(2) The time limit of melting Keep 3 suppositories in room temperature for 1h, determine in accordance with the apparatus and method of the disintegration test of tablets.Unle otherwise stated, fatty base suppositories must melt or soften in 30min, water-soluble base suppositories must diolve in water in 60min.

Experimental Instructions

Requirements for preview 1.To master physicochemical property of cocoa butter and the precautions when melt by heating.2.To master the precautions of preparation proce of glycerin-gelatin suppositories 3.To master the experimental method and calculation of displacement value (DV) 4.To design the procedures according to the teaching materials of the experiment.

Procedures and Precautions 1.When prepare the glycerol suppository, the water bath must keep boiling which will make stearic acid react with carbonic acid fully.Stop heating until the mixture turns into clarity and saponifying reaction complete.The chemical equation is as following.

2C17H35COOHNa2CO32C17H35COONaCO2H2O

The carbon dioxide generated by reaction must be thoroughly removed, and otherwise there will be bubbles in suppositories that may affect the appearance.The suppositories can also be prepared by heating sodium stearate and glycerol in the agitation directly that avoid saponifying reaction and improve the quality the suppositories.2.The glycerol suppositories contain plenty of glycerol (about 90-95%), which have the same effect of hypocatharsis as soda soap generated by saponifying reaction.3.The glycerin-gelatin comprises glycerol, gelatin and distilled water by certain proportion.The gelatin should be swelled in water to make it soft first so that it can be easily diolved by heating.Glycerin-gelatin is general used as the base of vaginal suppository.It is elastic, doesn’t liquate under body temperature but can diolve in body fluid gradually and release drug.The diolving rate can be affected by the proportion of glycerol, gelatin and distilled water.The bigger the ratio of glycerol or distilled water is, the faster diolving rate of glycerinated gelatin suppositories.4.Cocoa butter should be heated in the water bath below 36℃ in the preparation of tannic acid suppository in case that the crystal form of cocoa butter will transform.The melting point of the new crystal form decreases to 23~25℃ so it is difficult to solidify.Stir tannic acid and cocoa butter fully, keep stirring to transfer the mixture to the mold when it cools close to the solidifying point.The mold should keep in ice bath in advance so that the cocoa butter can solidify immediately which can avoid drugs deposit in the bottom of the mold of suppositories.5.Chlorhexide acetate is soluble in the ethanol, sparingly soluble in water (1.9:100).Tween 80 can help it uniformly disperse in glycerinated gelatin.

6.The displacement value should be considered to ensure accurate content of suppositories in the preparation of fatty bases of suppositories.The amount of bases of each suppository can be calculated by the following equation when the displacement value is known.

MEDf

Where M is the amount of bases, E is the amount of blank bases, D is dosage of each suppositories, f is the displacement value.6.Much foam can be produced from the reaction of sodium bicarbonate and acid citric when tinidazole is prepared into effervescent vaginal suppository.It can increase the contact surface of drug and mucous membrane so that the drug can permeate into the deep part of the fold of mucous membrane to play its drug action fully.The dosage of citric acid in the formulation is higher than theoretical dosage that is profit for killing or inhibiting infusorians and anaerobe as the vagina is in a tart condition.

Questions 1.What are the principles of preparation and precautions in the preparation of glycerol suppository?

2.What is the mechanism of action of glycerol suppository? 3.What is the meaning of displacement value according to the experiment?

4.What are the characteristics of glycerin-gelatin base in suppositories?