1. Suppository Development and Production
Marion Gold
Centerchem, Inc., Stamford, Connecticut.
Murti VePuri
Able Labs, South Plainfield, New Jersey
Lawrence H. Block
Duquesne University of, Pittsburgh, Pennsylvania

2. Introduction
Oral route of administration is the most acceptable and common compared with other routs of administration.
Oral route is not without limitations.
Some medication cause local stomach irritation.
Dose limitation.
Certain patients, children, elderly, and those with swallowing problems, are difficult to treat with oral tablets and capsules.
Target the medication to the affected area.
Ophthalmic, Nasal, Otic, Dermal, Vaginal and Anorectal tissues.

3. Suppositories The suppositories are the neglected dosage form.
Although lots of research done on this drug delivery system, there are continues to be a general rejection of the rectal delivery system.
There are important reasons to consider suppositories as a preferred route of administration in many situation.
The suppositories are the neglected dosage form.
Despite much work that has been done in recent years, especially in Europe and USA, there continues to be a general rejection of rectal delivery as a ely used route of administration.

4. Why the rectal route? When the patient is unable to use the oral route
Through, unconsuous, irritation in the stomach
When the drug is less suited to oral administration
Patient - * problem with GIT
* nauseous, postop eg unconscious, very young or old, mentally disturbed
Drug - * bad taste, GI irritation, unstable in GI pH or degraded, first pass effect

5. Definition
Solid or semisolid dosage forms used for rectal, vaginal, or urethral administration of therapeutic agents.

6. The dispersed phase can be incorporated into the suppository as:
Typically consist of dispersion of the active ingredient in an inert matrix generally composed of a rigid or semi-rigid base.
This matrix should be inert not to interact with the active ingredients and the excipients.
The dispersed phase can be incorporated into the suppository as:
Solid (Powder).
Liquid (either aqueous, alcoholic, or glycolic solutions, oils, extracts, etc.

7. Suppositories are available in a range of physical forms
The material for the base, are selected on the bases of its ability to soften, melt, or dissolve at body temperature.
Finished suppositories are manufactured in a variety of shapes and sizes to best suit the treatment requirements (nature of the active ingredients, site of administration.
Suppositories are available in
a range of physical forms
(molded or compressed,
foil or plastic wrapped, or gelatin
encapsulated.
The material for the base which can be either naturally or synthetically derived, is selected on the bases of its ability to soften, melt, or dissolve at approximately the temperature of the vagina or rectal.
Finished suppositories are manufactured in a variety of shapes and sizes to best suit the treatment requirements (nature of the active ingredients, site of administration, age and condition of the patient, desired release pattern.
Suppositories are available in a range of physical forms (molded or compressed, foil or plastic wrapped, or gelatin encapsulated.

8. Rectal administration & Applications
For local
Systemic drug delivery.

9. Drugs administered by rectal route
Local Effect
Astringents.
Anti-septics.
Local anaesthetics.
Vasoconstrictors.
Anti-inflammatory.
Soothing agents.
Protective agents.
laxatives
Systemic Effect
Analgesic & antipyretic.
Anti-inflammatory.
Anti-asthmatic.
Anti-convulsant.
Anti-emetic.
Nausea
Narcotic analgesia (Oxymorphone HCL)
Antihemorrhoidal suppositories –combination of astrin, local anaes, vasoconstrictors, analge, soothing and protective
Analgesic – oxymorphine
Antiinflamm – indomethacin
Antiemetic- prochlorperazine, ondansetron

10. Advantages Reduce hepatic first-pass elimination
Enhance drug bioavailability.
Alcoholic and aqueous solution can be rapidly absorbed, and this is used to considerable advantage, for example, to administer diazepam in the treatment of acute convulsive attacks.
This results from physiological differences in the venous drainage of the rectum; blood flow from the lower portion of the rectum, in contrast to that of the upper segment, does not immediately pass into the portal circulation and subsequently into the liver for enzymatic degradation. Instead, drugs absorbed from the lower rectum pass directly into the general circulation, and experiments have shown that increases in BE of as great as 100% over oral delivery are seen following rectal administration.

11. Comparison with Oral Delivery
Many studies have attempted to compare the oral dosage form with the rectal administration.
The results are inadequate, because of the different parameter used to make the studies, the experiment conditions and choice of excipient.
Certain active ingredients are just not well suited for suppository dosage.
Some experiments have been inconclusive in determining the relative superiority of indomethacin and aspirin when given by either of the two roots

12. Diazepam (as an alcoholic solution & propranolol have been shown to exhibit greater bioavailability when administered rectally.
Theophylline suppositories was found bioequivalence to oral administration when microcrystalline drug was used.
Bioequivalence between pentobarbital despite its slower rectal absorption.
In case where there is no first pass metabolism, it has been shown that rectal administration of drugs in solution can provide BE equivalent to that seen with oral administration.

13. Absorption of the materials is via passive diffusion; (no carrier-assisted means take part in the passage of drug through lipid membrane).
Thus, success or failure of therapeutic delivery is a function of lipo-solubility of the agent as well as its vehicle, because the partition coefficient of the drug between suppository base and the lumen contents influences the latter's release into the bowel and eventually the actives passage through the wall of the intestine.
Absorption of the materials is via passive diffusion; no carrier-assisted means take part in the passage of drug through lipid membrane. Thus, success or failure of therapeutic delivery is a function of lipo-solubility of the agent as well as its vehicle, because the partition coefficient of the drug between suppository base and the lumen contents influences the latter's release into the bowel and eventually the actives passage through the wall of the intestine.

14. Enhancement agents that affect the mucous membrane similarly affect absorption and are useful for boosting delivery of poorly absorbed agents such as antibiotics and high M.W materials.

15. The use of suppositories in the world
Rectal as well as urethral and vaginal delivery of drugs via suppositories makes excellent therapeutic sense, and there use can be traced as far back as in the writings of Hippocrates.
In Japan, rectal dosage forms are more acceptable by the patient than other route of administration.
More than 7.5% of all prescriptions in France were formulation intended for rectal administration.

16. Anglo-Saxon countries, where social convention preclude greater use of rectal delivery (generally do not prescribe suppositories).
Latin American and Mediterranean Europeans use suppositories far more routinely.
In summary the use of rectal suppositories is limited and are vary between nations.

17. Factors affecting the absorption from Rectal Suppositories
Physiological factors.
Physicochemical factors of the drug substance.
Physicochemical factors of the base.

18. 1. Physiological Factors
Colonic content.
Circulation route.
pH, and lack of buffering capacity of the rectal fluids.
1. When systemic effects are desired, greater absorption may be expected from a rectum that is void then from one that is distended with fecal matter. An evacuant enema could be use before the administration of a suppository.

19. Physiological Factors continued
Diarrhea, which case tissue dehydration of the rectum can influence the absorption.
Colonic obstruction due to tumorous growths, influence the rate and the degree of drug absorption from the rectal site.
2. Circulation Route, drugs absorbed rectally, bypass the portal circulation during their first pass into the general circulation

20. 3. pH and lack of buffering capacity of the rectal fluids.
The rectal fluids are neutral in pH (7-8), and have no effective buffering capacity.
The drug is administered will not generally be chemically changed by the rectal environment.
The suppository base used has major influence on the release of active constituents incorporated into it.

21. Physicochemical Factors
Includes:
Solubility of the drug in lipid and in water.
Particle size of dispersed drugs.
Physicochemical factors of the base include its ability to:
Melt.
Soften.
Dissolve at body temperature.
Release the drug substance,
and its hydrophilic or hydrophobic character.

22. Lipid-water solubility:
The lipid-water partition coefficient of a drug is an important factor in the selection of the suppository base and in drug release from that base.
A Lipophilic drug that is distributed in a fatty suppository base in low concentration has less of a tendency to escape to the surrounding aqueous fluids than the hydrophilic substance presents in a fatty base.
Water soluble base such as, PEG, which dissolve in the anorectal fluids, release for absorption both water soluble and oil soluble drugs.

23. Physicochemical Factors Continue…
Particle size:
Particle size of drugs present in the suppository in the undisclosed stat, the smaller the particle size the more readily the dissolution of the particles and the greater the chance for rapid absorption.
Nature of the base:
Melting point, softening, or dissolving to release its drug components for absorption, interacting with the drugs substance.

24. Ratio of Components
Once the correct excipient has been selected, the proper proportion of the components needs to be established.
One important aspect to consider in suppository formulation is that of displacement.
Suppositories generally weigh between 1 to 4 g, and displacement of the excipient by the active ingredient must be calculated when the product is formulated.

25. Simply, this step takes into account the volume of suppository base that will be displaced by an insoluble drug dispersed into it.
This is necessitated by the practice of placing weighed quantities of suppository ingredients into molds whose contents are measured volumetrically.

26. M = F - (f * S)
M = the quantity (weight) of suppository base needed. F = the total capacity of the suppository mold. f = the displacement factor of the active ingredients. S = the quantity of the active ingredient per suppository.

27. Calculation of Displacement Value
M = the quantity (weight) of suppository base needed.
F = the total capacity of the suppository mold.
f = the displacement factor of the active ingredients.
S = the quantity of the active ingredient per suppository.

28. Displacement Value
The volume of a suppository from a particular mould is uniform.
The weight is vary according to the density of the medicaments.
The displacement value of a drug is the number of parts by weight of drug which displaces one part by weight of the base.
Could be calculated and could be found in the literature.

29. Displacement Factors of Selected Materials
Acetylmorphine Hydrochloride
0.71
Acetylsalicylic acid
0.63
Beeswax
1.0
Benzocaine
0.68
Bismuth subgallate
0.37
Bismuth sbnitrate 0.33
0.33
Codeine phosphate
0.8
Glycerin
0.78
Phenacetin
0.6
Phenobarbital
0.84
Phenobarbital sodium
0.62
Procaine
Quinine chlorohdrate
0.83
Sulfamide
Theophylline
Zinc oxide
0.2

30. Formulation Choice of drug:OK
Choice of drug:
What makes a particular drug a candidate for
administration in the form of a suppository?
It must be sufficiently absorbed through the rectal mucosa to permit therapeutic blood levels.
Drug that are poorly absorbed after oral dosage.
Drugs that cause irritation to the gastrointestinal mucosa.
Certain antibiotics cause major changes to the balance of intestinal flora, and there would be better given as suppositories.
Choice of drug:
What makes a particular drug a candidate for
administration in the form of a suppository?
It must be sufficiently absorbed through the rectal mucosa to permit therapeutic blood levels to be reached. (some time we need to use “promotion adjuvant”
Drug that are poorly absorbed after oral dosage.
Drugs that cause irritation to the gastrointestinal mucosa.

31. Small polypeptides-normally subject to the enzymatic activity of the upper GIT, can often be better administered via the rectum.
The pH of the upper GIT causes inadequate or otherwise undesirable uptake.
For local conditions achieved using a suitable suppository formulation. OK
Certain antibiotics cause major changes to the balance of intestinal flora, and there would be better given so as to bypass this portion of the gut.
Small polypeptides-normally subject to the enzymatic activity of the upper GIT, can often be better administered via the rectum.
The pH of the upper GIT causes inadequate or otherwise undesirable uptake, and the possibility of avoiding this problem by using lower colorectal introduction is highly desirable.
For local conditions achieved using a suitable suppository formulation.

32. The actives physical state under ambient conditions. NO
Nature of the active.
Three principal factors that define formulation
requirements:
The actives physical state under ambient conditions.
The solubility characteristics of the active.
The physicochemical activity with regards to potential excipients.
As is the case with any dosage form, the physical nature of the active together with its chemical behavior largely governs many aspects of product development. Three principal factors that define formulation requirements are the actives physical state under ambient conditions, its solubility characteristics, and finally its physicochemical activity with regards to potential excipients.

33. The active can be either liquid, pasty, or solid in nature.
Physical State.
The active can be either liquid, pasty, or solid in nature.
Bulk Density. the big difference in the density between the active and the base cause problem during filling and homogeneity of the suppositories.
Solubility: NO
In solid the particle size is essential to increase the BE of the suppositories by increasing the surface area and hence increasing the dissolution rate.
The solid can affect adversely the product by thickening the active excipient mix., which case problem in the flow ability of the active mix during filling.
Bulk Density: the big difference in the density between the active and the base
Solubility: the degree if any to which the active ingredients is soluble in the excipient influences manufacture in several ways.
For example, increased solubility of the active in the suppository base helps to improve product homogeneity, but at the same time it diminishes the release of the active if there is too great a propensity for it to remain in the excipient. This can be used advantageously within limits; one function of a suppository is to maintain a drug at its target site, and a controlled affinity of the suppository is to maintain a drug at its target site, and controlled affinity of the active for the excipient can be governed by the degree of miscibility of the two suppository components. From a formulators point of view, solubility of the active in the base represents a rather straightforward situation: the principal point to consider is that the melting point of the base will be lowered after addition of the active, so that t base with a higher melting point should be used. However, suppository crystallinity and subsequently hardening and product cohesion is affected, and should be assessed during formulation trials.
On the other hand, insolubility of the active in the excipient necessitates treatment of the mix as an emulsion or suspension; that is , handling as a dispersion, a more difficult problem. In this situation, it is necessary to maintain product homogeneity of two phases within the product melt.
A number of standard approaches to emulsification can be used; all however, must be reviewed in light of their potential irritation to the rectal mucosa. Thus, certain surfactants entirely acceptable for other uses cannot be considered for this application. Usually, the problems can be readily resolved with the addition of appropriate emulsifying agents such as polysorbate to suppository base, and indeed, some manufactures provide bases pre-formulated with these material. As a further assurance of product homogeneity, continuous agitation of the melted active/base just to the point of pouring into the mold.

34. B. Choice of the Base NO
They enable a selected active to be fabricated in a manner appropriate to both its physicochemical characteristics and the requirements of the manufacturer.
They are used to control delivery of the medication at its site of absorption.
For this reason the bases manufacturers offer a wide selection of raw materials in order to anticipate a correspondingly broad range of product needs.

35. Selection criteria of the baseNO
Nature of the active ingredient.
Manufacturing capabilities.
Desired release characteristics.
Chemical no-reactivity with the active.
Nontoxic and nonirritant, and stable when formulated.

36. Selection of the appropriate Base
During Production:
Slight contraction upon cooling in order to facilitate removal from the mold.
Inertness no chemical interaction between the base and the active ingredients.
Solidification (should be optimum).
Viscosity: to be viscose to prevent sedimentation during filling until cooling.
Rather than simply being inert vehicles, suppository bases serve several functions during defferent phases of suppository manufacture and distribution and selection of the base must encompass the following consideration.
To each stage of a suppository life the inherent characterisstics of the base determine relative success or failure of the finished products.

37. During Storage: Impurity.
Bacterial/Fungal contamination should be minimized by selecting a non-nutritive base with minimal water content.
Softening.
The suppositories should be formulated so that it does not soften or melt under transportation and storage conditions.
Stability.
The selected materials can not oxidize when exposed to air, humidity, Or light. NO

38. NO
During Use:
Release.
Choice of the proper base provides optimal delivery of the dispersed active into the target site.
Tolerance.
The finished suppository should have minimal toxicity and not be irritating to sensitive rectal mucosal tissue.

39. Suppository Basis
Suppository bases plays an important role in the release of the drug they hold and therefore in the availability of the drug for absorption for systemic effects or for local action.
And because of the possibility of chemical and or physical interactions between the drug and the base, which could affect the stability and or bioavailability of the drug, the absence of any drug interaction between the two agents should be ascertained before formulation

40. Suppository Bases
From the point of view of composition, suppository bases can be described as falling into one of the three categories:
Naturally derived.
Synthetic.
Semisynthetic.

41. I. Natural Bases
All naturally derived suppository bases used today are produces from Cocoa Butter, it’s a fatty material composed of a mixture of C16 to C18 saturated and unsaturated fatty acid triglycerides obtained from the roasted seed of Theobroma cacao.
Fatty bases are the most frequently used suppository bases.
These bases melt at body temperature.

42. In addition to cocoa butter, other natural materials such as:
Gelatin, Agar, and Waxes have been employed as suppository bases.
Their uses are limited and often relegated to special applications because special problems are encountered with their use.

43. Advantages:
It is readily liquefies on heating but sets rapidly when cooled down.
Melt at body temperature.
It is miscible with many ingredients.
It is bland, therefore no irritation occurs.

44. Disadvantages:
Despite Theobroma oil been used for over 200 years, however it is not without limitations.
And those limitations are:
Theobroma oil is polymorphic i.e. when it is heated and cooled it solidifies in a different crystalline form.
Theobroma oil shrinks slightly on cooling,
adherence to the walls of suppository mold.
The relatively low melting point makes it unsuitable for use in hot climates.

45. The melting point is reduced if the active ingredients are soluble in the base.
Theobroma oil deteriorates on storage and is prone to oxidation.
The quality of Theobroma oil may vary from batch to batch, and it can be expensive.
For these reasons, the use of cocoa butter as a suppository base is becoming increasingly less attractive, particularly in the of the availability of more modern alternatives.

46. II. Synthetic & Semi-synthetic Bases
Chemically they are usually derivatives of fatty acids that undergo chemical alteration (transesterification) to enhance their use for this application
Such chemical reactions yield a range of products with controllable characteristics making them suitable to be used as suppository bases.
These bases are produced from vegetable fats and oils that are chemically modified during their manufacture

47. For example:
Hydrogenation is typically carried out to improve stability (enhance stability to oxidation and to increase chemical inertness).
Hydrogenating suitable vegetable oils such as
(Palm kernel oil and cottonseed oil) are used.
Melting point ranges can be more precisely tailored to specific requirements.
Examples of semisynthetic suppository bases: Novata, Suppocire, Wecobee and Witepsol types.
As can the relative oil-water solubility.

48. Advantages: The base is more flexible and not brittle.
More stable on oxidation and hydrolysis.
Less irritant compare with other bases.

49. Disadvantages
The viscosity of the synthetic fats, when melted, is lower than that of Theobroma oil. this may lead to.
Sedimentation risk of the active ingredients during the preparation process.
Lack of uniformity of the active ingredients.
These bases become very brittle if cooled too rapidly, so should not be refrigerated during the preparation period.
There is more than one grade of synthetic fatty basis.

50. Water soluble & water miscible bases
Glycerol-gelatin bases:
These bases is a mixture of glycerol and water, which is stiffened with gelatin.
Mass of Glycerol suppositories BP has 14% w/w gelatin and 70% w/w glycerol.
In hot climates gelatin content can be increased to 18%.
Gelatin is purified protein produces by the hydrolysis of the caliginous tissue of animals such as skins and bones.
There is two types of gelatin: Type A and Type B.

51. Disadvantages of this type of bases:
This type of base is less frequently used than the fatty bases for a variety of reasons.
Disadvantages of this type of bases:
Glycerol-gelatin base have a physiological effect.
This is useful if a laxative effect is required but otherwise is undesirable.
Difficulties in preparation and handling.
The dissolution time depends on the content and quality of the gelatin and also the age of the suppository.
Glycerol-gelatin base have a physiological effect. They dissolve in the mucous secretions of the rectum but, because of the small amount of liquid present, osmosis occurs.

52. They are hygroscopic and therefore require careful storage and may cause rectal irritation.
Possibility of microbial contamination is more likely than with the fatty bases.

53. Macrogols
These are different types of polyethylene glycols which are blended together to produce suppository bases which vary in:
Melting point.
Dissolution rates.
Physicochemical characteristics.
High polymer produce preparation which release the drug slowly (they are brittle).
A combination of different polymer release the drug more readily can be prepared by mixing high polymers with medium and low polymers. (Less brittle)

54. Drug is release as the base dissolves in the rectal contents.
Advantages:
They have no physiological effect, e.g. do not produce a laxative effect.
They are not prone to microbial contamination.
Some polymers have a high melting point.
They have a high water-absorbing capacity.
In solution, viscosity is high, which means there is less likelihood of leakage from body.

55. Disadvantages:
They are hygroscopic which means they must be carefully stored.
They are incompatible with several drugs and materials, e.g. bnzocaine, penicillin and plastic.
They become brittle if cooled too quickly and also may become brittle on storage.
Crystal growth occurs with some active ingredients.

56. Hydrogels
Currently, an alternative vehicle for rectal delivery is being actively investigated.
Hydrogels are among them, and it defined as macromolecular networks that swell, but do not dissolve, in water.
The swelling of hydrogels, i.e., the absorption of water, is a consequence of the presence of hydrophilic functional groups attached to the polymeric network.
The aqueous insolubility of hydrogels results from the cross-links between adjacent macromolecules.
Currently, and alternative vehicle for rectal delivery is being actively investigated.
Hydrogels defined as macromolecular networks that swell, but do not dissolve, in water. The swelling of hydrogels, i.e., the absorption of water, is a consequence of the presence of hydrophilic functional groups attached to the polymeric network. The aqueous insolubility of hydrogels results from the cross-links between adjacent macromolecules. The use of hydrogel matrix for drug delivery involves the dispersal of the drug in the matrix, followed by drying of the system and concomitant immobilization of the drug.

57. The use of hydrogel matrix for drug delivery involves the dispersal of the drug in the matrix, followed by drying of the system and simultaneous immobilization of the drug.
When the hydrogel delivery system is placed in an aqueous environment, e.g., the rectum, the hydrogel swells, and drug is then able to diffuse out of the macromolecular network.

58. Selection Criteria Melting Temperature Range. Iodine Value.
Hydroxyl Index.
Specification for the melting tem of suppository bases define a melting temperature range rather than a single point. This practice is not due to inadequate controls but rather to the range of tem between the stable and unstable forms, a result of the polymorphism existence in several crystalline states of these materials. when a base is selected on the basis of its melting tem, one should keep in mind that the range offered by a manufacturer has been designed to provide flexibility for working within a particular active ingredient/therapeutic requirement framework. For example, the incorporation of a liquid agent into a base will generally tend to decrease the final melting tem of the finished suppository, so that selection of a higher melting tem base is advised.. Similarly,
inclusion of large quantities of fine powders will bring about an increase in product viscosity, requiring a abase with lower melting temperature.
Iodine Value:
Rancidification (Oxidation) of suppository base can be more of a problem than with other dosage forms. Because of the sensitivity of rectal mucosal tissue, and the possibility of its extended exposure to the melted suppository base, potentially irritating antioxidants are generally not advised for incorporation into suppositories. To avoid their use, bases with iodine values less than 3 (and preferably less than 1) should be employed exclusively.
Hydroxyl Index:
The determination of the hydroxyl index reveals the presence of mono-and di-glycerides in a particular substance and indicates its relative rate of crystallization. In general, a lower value permits a faster rate of suppository manufacture. Materials possessing a low hydrroxy index also provide better stability in cases where the active ingredient is sensitive to the presence of the hydroxyl group.

59. Suppository Production Methods
Melting.
Compression.
Injection.
Injection molding production process involving PEGs as the base might proceed as follows:
The PEGs are first melted and mixed in a vessel equipped with a stirrer and a heating device at about 60°C to 80°C .

60. Additional viscosity -plasticity –adjusting ingredient, auxiliary ingredients, and actives are added while stirring.
Once blending is complete, the melt is extruded into precision-machined multi-cavity molds.
Rapid solidification of the melt is followed by ejection of the molded units from the mold cavities.
Very fast,
Precise metering and molding.
Range of shapes and sizes

61. In-Process Control
Proper monitoring of product physical characteristics is necessary to ensure that the production process remains under control throughout filling.
Visual Examination: Examination of physical defects of finished suppositories provides valuable information for process monitoring. Color variations, chips, cracks, depressions, and surface irregularities are evidence of problems that require attention.

62. Weight checks: periodic weighing of individual suppositories will reveal problem in the filling operation. (in each filling needle).
Leak Test
The quality of the seal is a parameter that can affect the stability of the product (vacuum test).

63. Quality Control A. Physical Analysis:
Visual Evaluation, surface appearance and color can be verified visually to assess:
Absence of fissuring, pitting, fat blooming, exudation, and migration of the active ingredients.
The last test accomplished by taking a longitudinal section of the suppository to verify the homogeneity of the active ingredients within the mass.

64. 2. Melting Point.
The melting point is a critical factor in the determination of the release rate of the active ingredients from the suppository.
The melting point of the finished suppository should generally; not be greater than 37°C.

65. 3. Liquefaction Time.
This is an important element indicates the physical behavior of a suppository subjected to its maximum functional temperature 37°C.
It measures the time necessary for a suppository to liquefy under pressures similar to those found in the rectum (30g) in the presence of water at body temperature.
A rule of thumb is that liquefaction time should be no longer than 30 minutes.

66. 4. Mechanical strength:
This is the determination of the mechanical force necessary to break a suppository, and it indicates whether a suppository is brittle or elastic.
The mechanical strength should in no case be less than 1.8 to 2 kg.

67. 5. Melting and Solidification:
The most commonly used methods are:
Open capillary tube.
U-Tube.
Drop Point.
These methods are similar in principle, differ somewhat in their methodologies. all require the introduction of a sample into a specified place in the apparatus, after which heat is applied in a controlled manner.
Means are provided for the determination of the point at which the test material undergoes a change in physical state, (i.e., melts).

68. An ideal suppository base must:
Melt at or just below body temperature or dissolve in body temperature.
Solidify quickly after melting.
Be miscible with many ingredients.
Be bland, i.e. non-toxic and non-irritant.
Be stable on storage.
Be resistant to handling.
Be stable to heating above its melting point.
Release the active ingredients readily.
Be easily molded and removed from the mold.

69. Release Process of drug from suspension suppository
Melting and Spreading
Sedimentation
Wetting
Dissolution

70. Factors affecting drug release process
Temperature
Contact area
Release medium
Movements
Membranes

71. Formulation of suppositories
Different types – rectal, vaginal, and urethral.
Different shapes and sizes
Usually between 1-4g
Drug content varies widely – 0.1% to 40%
Vehicle (base) in which drug is incorporated – sometimes contain other additives

72. Mould Calibration
The capacity of the mould is determined by filling the mould by the chosen base.
The total weight of the perfect product is taken and a mean weight calculated.
This value is the calibration value of the mould for the particular base.

73. Melt 2/3 of the base and then remove form the heat, the residual heat will melt the rest of the base.
Reduce the particle size of the active ingredients.
Weigh the correct amount of medicament and place on a glass tile.
Add half of the molten base to the powdered drug and rub together with a spatula.
Scrape this mixture off the tile, using the spatula and place back into the porcelain basin.
Quickly pour into the mould, slightly overfilling each cavity.
Leave the mould and its contents to cool for 5 min.
Allow to cool for further min.
Unscrew the mould and remove the suppositories.

74. Packaging and Storage Plastic (PVC) or aluminium foil pack
Protection against moisture and oxygen
Store in cool place
High humidity – absorb moisture – spongy
Low humidity – lose moisture - brittle