Chapter 12

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Suppositories

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suppositories:

1 suppositories By ARUNKUMAR B. WALIKAR M.PHARM DEPARTMENT OF PHARMACEUTICS B.L.D.E.A’s S S M COLLEGE OF PHARMACY, VIJAYPUR

contents:

contents Introduction Classification of suppositories Advantages & disadvantages Ideal properties of suppositories Formulation of suppositories Preparation of suppositories Evaluation & packing of suppositories 2

Introduction:

Introduction Suppositories are the solid dosage forms meant to be inserted into the body cavities other than the mouth like rectum, urethra and vagina where they melt or soften to release the drugs and exert local or systemic effects. 3

Classification Of Suppositories:

Classification Of Suppositories Rectal suppositories Vaginal suppositories ( PESSARIES ) Urethral suppositories ( BOUGIES ) Nasal suppositories Ear suppositories or ear cones(Aurinaries) 4

VAGINAL SUPPOSITORY :

VAGINAL SUPPOSITORY They are also called as PESSARIES. SHAPE : globular, oviform or cone-shaped. Weigh about 3-5gm Used occasionally. Intended for local effects like contraceptives, Antifungal, antiseptics drugs in feminine hygiene 5

URETHRAL SUPPOSITORY :

URETHRAL SUPPOSITORY Also called as BOUGIES . SHAPE – slender, pencil-shaped. Weight: For females they weight about 2g and are 60-75mm long and 5mm in diameter. For males they weight about 4g and are 100-150mm long and 5mm in diameter Intended for anti-bacterial or as a local anesthetic preparative for urethral examination and also erectile dysfunction. Occasionally used. 6

RECTAL SUPPOSITORY:

RECTAL SUPPOSITORY Shape: Cone or torpedo shape. Weight: For children's weigh about 1gm and diameter of 3-6mm. For Adults weigh about 2gm and diameter of 3-6mm. Intended for local action to relieve constipation, irritation, itching and inflammatory associated to hemorrhoids 7

NASAL SUPPOSITORY:

NASAL SUPPOSITORY Shape: They are thin cylindrical in shape Weigh: Around 1gm Base used: Glycero -gelatin base Used occasionally. Intended for Anti-inflammatory and anti-allergic drugs 8

EAR CONE (Aurinaries):

EAR CONE (Aurinaries) Shape: They are long cylindrical in shape Weigh: Around 1gm Base used: Glycero-gelatin base Used occasionally. Eg : Waxylone 9

Classification Of Suppositories Via Position Of Action :

Classification Of Suppositories Via Position Of Action LOCAL EFFECT : In case of pain, itching and hemorrhoid. Locally active drugs include astringents, antiseptics, local anesthetics, vasoconstrictors, anti-inflammatory, soothing and protective agents and some laxatives. SYSTEMIC EFFECT : Anti-asthmatics, anti rheumatics, anti-pyretic and analgesics 10

ADVANTAGES:

ADVANTAGES EASILY ADMINSTERED to children, old persons, to unconscious or sometimes to mentally unstable persons who cannot swallow the drug. Convenient mode of administration for drugs which irritate the GIT, causing vomiting and destroyed in acidic pH of stomach and enzymes of GIT. FASTER ONSET OF ACTION as compared to oral administration because absorption of drug through rectal mucosa directly reaches blood 11

DISADVANTAGES:

DISADVANTAGES They are not acceptable by the patients. The manufacturing process is difficult. The drugs which cause irritation to the mucous membrane cannot be administered as suppositories. Most of the suppositories should be stored at low temperature10-20°c in a refrigerator , other wise the base gets liquified. Leakage of the suppositories occurs upon insertion into the body cavity at elevated temperature. 12

IDEAL PROPERTIES OF SUPPOSITORY BASES:

IDEAL PROPERTIES OF SUPPOSITORY BASES It should melt at body temperature or dissolve or disperse in body fluids. It should release any medicament easily. It should keep its shape when being handled. It should be non-toxic and non-irritant to the mucous membrane. It should be stable on storage and also stable if heated above its M.P. 13

IDEAL PROPERTIES OF SUPPOSITORY BASES:

IDEAL PROPERTIES OF SUPPOSITORY BASES It should be easily molded and should not adhere to the mold. It should possess good wetting and emulsifying properties. It should be able to incorporate a high percentage of water. It should be chemically and physically stable 14

Formulation of suppositories:

Formulation of suppositories Bases Anti- oxidants Emulsifying agents Hardening agents Preservatives Thickening agents Plasticizers 15

SUPPOSITORY BASES:

1. Hydrophilic bases: these are the one which have the ability to absorb additional water in the preparation. They are of two types water-dispersible bases: properties: These are mixtures of non-ionic surfactants which are chemically related to polyethylene glycols. These are used alone or in combination with other types of bases Cellulose derivatives like methylcellulose sodium carboxy methylcellulose also come under this class. Eg ; polyoxyethylene sorbitan fatty acid ( tween ) 16 SUPPOSITORY BASES

ii)Water soluble bases: :

ii)Water soluble bases: Glycerinated gelatin or Glycero -gelatin : This occurs as a gel .It is a mixture of gelatin, glycerol and water. According to B.P the composition of the base is gelatin-14%w/w ,glycerol-70%w/w To get a stiff mass, the quantity of gelatin should be increased to32%w/w and that of glycerol reduced to 40%w/w. 17 Glycerinated gelatin Polyethylene glycol (PEG) polymers.

Slide18:

18 A- Glycerinated Gelatin Glycerinated Gelatin is a useful suppository base, particularly for vaginal suppositories , where the prolonged localized action is usually desired. Glycerinated gelatin suppositories are translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly in mucous secretions to provide prolonged release of active ingredients. It is suitable for use with a wide range of medicaments including alkaloids, boric acid, and zinc oxide.

Slide19:

19 Suppositories made with glycerinated gelatin must be kept in well-closed containers in a cool place since they will absorb and dissolve in atmospheric moisture. Suppositories may have a dehydrating effect and be irritating to the tissues upon insertion . The water present in the formula of suppositories minimizes this action and the suppositories may be moistened with water prior to insertion to reduce the tendency of the base to draw water from mucous.

Slide20:

20 In addition, those suppositories intended for extended shelf-life should have a preservative added, such as methylparaben or propylparaben, or a suitable combination of the two. To facilitate administration, glycerinated gelatin suppositories should be dipped in water just before use .

Slide21:

21 Preparation of glycerinated gelatin rectal suppositories Mix or dissolve the medicaments in water to make a total of 10 g. Add 70 g of glycerin and mix. Add 20 g of granular gelatin, mix carefully to avoid incorporation of air. Heat on a steam bath until the gelatin is dissolved. Pour the melted mixture into molds and allow to congeal.

Slide22:

22 Preparation of glycerinated gelatin urethral suppositories The gelatin constitutes about 60% of the weight of the formula, the glycerin about 20%, and the medicated aqueous portion about 20%.

Slide23:

23 B- Polyethylene Glycol Polymers Polyethylene Glycol Polymers have received much attention as suppository bases in recent years because they possess many desirable properties. They are chemically stable, nonirritating, miscible with water and mucous secretions , and can be formulated, either by molding or compression, in a wide range of hardness and melting point.

Slide24:

24 Like glycerinated gelatin, they do not melt at body temperature, but dissolve to provide a more prolonged release than theobroma oil. Certain polyethylene glycol polymers may be used singly as suppository bases but, more commonly, formulas call for compounds of two or more molecular weights mixed in various proportions as needed to yield a finished product of satisfactory hardness and dissolution time.

Slide25:

25 PEGs having average molecular weights of 200, 400 and 600 are clear, colorless liquids. Those having molecular weights of greater than 1000 are wax-like, white solids with hardness increasing with an increase in the molecular weight. Since the water miscible suppositories dissolve in body fluids and need not be formulated to melt at body temperature, they can be formulated with much higher melting points.

Slide26:

26 This property permits a slower release of medicaments from the base, safe storage at room temperature without need for refrigeration, and ease and slow insertion. To prevent irritation of the mucous membranes after insertion of PEGs suppositories, they should contain at least 20% of water or dipped in water just prior to use.

Slide27:

27 Examples of various PEGs used in suppository bases 1450 8000 300 8000 30% 70% 60% 40% 300 6000 1000 3350 1000 3350 48% 52% 95% 5% 75% 25%

2. Oleaginous Bases (Fatty) 0r Lipophilic Bases :

2. Oleaginous Bases (Fatty) 0r Lipophilic Bases Coca butter: Properties: It is a natural triglyceride It can exist in more than one crystalline form i.e., it exhibits polymorphism It consists of mixture of oleic acid , palmitic acid , stearic acid . 28

Slide29:

29 If the base is fatty, it has the following additional requirements: Acid value is below 0.2. Saponification value ranges from 200 to 245. Iodine value is less than 7. The interval between melting point and solidification point is small.

Slide30:

30 A- Theobroma Oil or cocoa butter Theobroma Oil or cocoa butter is used as a suppository base because, in large measure, it fulfills the requirements of an ideal base. Cocoa butter is primarily a tri-glyceride, it is yellowish- white, solid, brittle fat, which smells and tastes like chocolate. At ordinary room temperatures of 15° to 25°C it is a hard, amorphous solid, but at 30° to 35°C i.e., at body temperature, it melts to a bland, nonirritating oil.

Slide31:

31 Thus in warm climates, theobroma oil suppositories should be refrigerated. Cocoa butter has iodine value between 34 and 38. Its acid value not higher than 4.

Slide32:

32 Disadvantages of theobroma oil Shrinks only slightly on solidification; a mould lubricant is therefore required. Exists in four polymorphic forms with different melting points (18.9, 23.0, 28.0, and 34.5ºC). Theobroma should only be heated for a short time and at temperatures below 36 ºC in order to minimize the formation of the unstable low melting point forms.

Slide33:

33 The change (reduction) in melting point caused by addition of certain drugs such as volatile oils, phenol or chloral hydrate to cocoa butter suppositories. The solution is to raise the melting point back to the desired range by addition of 3% to 5% of beeswax or spermaceti. Theobroma oil has a low absorptive capacity for water, but this can be increased by adding surfactants such as cholesterol 2%, emulsifying wax up to 10%, polysorbates 5 to 10%, or wool fat 5 to 10%. However, the addition of surfactants may lead to a drug- base interaction or affect the release of drug from suppository.

Slide34:

34 Theobroma oil is prone to oxidation (due to high iodine value); this can be partly overcome by storage in a cool, dark place. Theobroma oil may vary in consistency, odor, and color depending on its source like other natural products. The low melting point of theobroma oil may pose storage problems in hot climates.

Slide35:

35 3. Miscellaneous Bases Chemical or physical Mixtures of oleaginous and water soluble or water miscible materials. Emulsions, generally of w/o type (i.e. mixing of cocoa butter with emulsifying agents). Polyoxyl 40 stearate is a mixture of the mono-stearate and di-stearate esters of mixed poly-oxyethylene diols and the free glycols. Soap may be used as a base (i.e. Glycerin suppositories, USP, with soap as the base).

2.Anti-oxidants:

2.Anti-oxidants They protect the drug and the base from getting degraded due to oxidation. Examples : Ethyl or propyl gallate Ascorbic acid and its esters Hydroquinone Tocopherols 36

3.Emulsifying agents: :

3.Emulsifying agents: They increase the water-absorbing capacity of fatty bases. This makes it possible to include aqueous solutions in the formulation. Examples : polysorbates ( tween 60) Wool alcohol ,wool fat Hardening agents : These are included in those formulations where the melting point of the base is decreased by the drug. 37

Slide38:

38 These agents bring the melting point to normal. Examples : macrogols with high molecular weight. 5.Preservatives : They should be included in suppositories which contain water soluble bases to prevent microbial growth. Examples :methyl paraben , propyl paraben 6.Thickening Agents: They increase the viscosity of molten base and prevent sedimentation of suspended insoluble solids. Examples: Aluminium monostearate , collodial silica ,magnesium stearate .

7.Plasticizers ::

7.Plasticizers : They impart plasticity to the fatty base and makes it less brittle. Examples : Castor oil Glycerine or propylene glycol Glycol Tween 80 Tween 85 39

METHODS OF PREPARATION:

METHODS OF PREPARATION Four methods Suppositories can be extemporaneously prepared by one of four methods. Molding by hand or Hand Rolling Compression Fusion Molding or Pour molding Compression in a tabletting machine 40

Slide41:

41 It is the oldest and simplest method of suppository preparation and may be used when only a few suppositories are to be prepared in a cocoa butter base. It has the advantage of avoiding the necessity of heating the cocoa butter. A plastic-like mass is prepared by triturating grated cocoa butter and active ingredients in a mortar. 1. Hand Rolling or MOLDING BY HAND

Slide42:

42 The mass is formed into a ball in the palm of the hands, then rolled into a uniform cylinder with a large spatula or small flat board on a pill tile. The cylinder is then cut into the appropriate number of pieces which are rolled on one end to produce a conical shape. Effective hand rolling requires considerable practice and skill. The suppository "pipe" or cylinder tends to crack or hollow in the center, especially when the mass is insufficiently kneaded and softened. MOLDING BY HAND

MOLDING BY HAND:

MOLDING BY HAND Hand molding is useful when we are preparing a small number of suppositories 43 STEP 1 drug fine powder

MOLDING BY HAND :

MOLDING BY HAND 44 STEP 2 Drug (fine powder) base

MOLDING BY HAND:

45 MOLDING BY HAND STEP 3 Trituration in mortar and pestle

MOLDING BY HAND :

MOLDING BY HAND 46 STEP 4 Mass Rolled Long rods

MOLDING BY HAND:

47 MOLDING BY HAND STEP 5 Rods cut into pieces

Slide48:

48 2. Compression Molding Compression molding is a method of preparing suppositories from a mixed mass of grated suppository base and medicaments which is forced into a special compression mold using suppository making machines. The suppository base and the other ingredients are combined by thorough mixing. The friction of the process causing the base to soften into a past-like consistency.

Slide49:

49 On a small scale, a mortar and pestle may be used (preheated mortar facilitate softening of the base). On large scale, mechanically operated kneading mixers and a warmed mixing vessel may be applied. In the compression machine, the suppository mass is placed into a cylinder which is then closed. Pressure is applied from one end to release the mass from the other end into the suppository mold or die. Compression Molding…..

Slide50:

50 When the die is filled with the mass, a movable end plate at the back of the die is removed and when additional pressure is applied to the mass in the cylinder, the formed suppositories are ejected. The end plate is returned, and the process is repeated until all of the suppository mass has been used. Compression Molding…..

Slide51:

51 The method requires that the capacity of the molds first be determined by compressing a small amount of the base into the dies and weighing the finished suppositories. When active ingredients are added, it is necessary to omit a portion of the suppository base, based on the density factors of the active ingredients. Compression Molding…..

2.COMPRESSION MOLDING:

2.COMPRESSION MOLDING The cold mass of the base containing the drug is compressed into suppositories using a hand operated machine. 52 STEP 1 drug fine powder

COMPRESSION MOLDING :

COMPRESSION MOLDING 53 STEP 2 Drug (fine powder) Base

COMPRESSION MOLDING :

COMPRESSION MOLDING 54 STEP 3 Trituration in pestle and mortar

COMPRESSION MOLDING :

COMPRESSION MOLDING 55 STEP 4 Compress the mixture in the compression mold

Slide56:

56 3. Fusion Molding Fusion Molding involves: 1- Melting the suppository base 2- Dispersing or dissolving the drug in the melted base. 3- The mixture is removed from the heat and poured into a suppository mold. 4- Allowing the melt to congeal 5- Removing the formed suppositories from the mold. The fusion method can be used with all types of suppositories and must be used with most of them.

Slide57:

57 Suppository molds Small scale molds are capable of producing 6 or 12 suppositories in a single operation. Industrial molds produce hundreds of suppositories from a single molding.

Slide58:

58 Lubrication of the mold Depending on the formulation, suppository molds may require lubrication before the melt is poured to facilitate the clean and easy removal of the molded suppository. Lubrication is seldom necessary when the suppository base is contracting sufficiently on cooling. Lubrication is usually necessary when glycerinated gelatin suppositories are prepared.

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