1 / 75
E N D
SUPPOSITORIES AND PESSARIES NAGAM SANTHI PRIYA Department of pharmaceutics
CONTENTS • Introduction • Classification of suppositories • Advantages & disadvantages • Ideal properties of suppositories • Formulation of suppositories • Preparation of suppositories • Evaluation & packing of suppositories
Introduction • Suppositories are the solid dosage forms meant to be inserted into the body cavities like rectum , urethra and vagina ,where they melt or soften to release the drugs and exert local or systemic effects.
Anatomy and Physiology of Rectum • The rectum is about 15 to 20 cm long. • It hooks up with the sigmoid colon to the north and with the anal canal to the south. • It is a hollow organ with a relatively flat wall surface, without villi and with only three major folds, the rectal valves
Anatomy and Physiology of Rectum • The terminal 2 to 3 cm of the rectum is called the anal canal. • The opening of the anal canal to the exterior is called the anus. • The anus is controlled by an internal sphincter of smooth muscle and an external sphincter of skeletal muscle.
Anatomy and Physiology of Rectum • Under normal conditions, the rectum is empty and filling provokes a defecation reflex which under voluntary control. • The transverse folds in rectum keep stool in place until the person is ready to go to the bathroom. Then, stool enters the lower rectum, moves into the anal canal, and then passes through the anus on its way out. • Rectum contains about 2 to 3 ml of mucous, which has a pH of 7.4 and little buffering capacity.
Absorption of drugs from the rectum • Medicaments absorbed in the lower part of the rectum are delivered directly into the systemic circulation, thus avoiding any first-pass metabolism. • However, it has been found that suppositories can settle high enough in the rectum to allow at least some drug absorption into the superior vein. • Thus keeping the drug in the lower part of the rectum would be advisable.
Absorption of drugs from the rectum • Insertion of a suppository into the rectum results in a chain of effects leading to the bioavailability of the drug. • Depending on the character of the base, a suppository will either dissolve in the rectal fluid or melt on the mucous layer. • Since the volume of rectal fluid is so small, complete dissolution of the base require extra water.
Absorption of drugs from the rectum • Due to osmotic effects of the dissolved base, water is attracted with a painful sensation for the patient. • Independent on the base type, dissolved drugs in the suppository will diffuse out towards the rectal membrane. • The process of absorption will be passive diffusion.
Classification Of Suppositories • Rectal suppositories • Vaginal suppositories ( PESSARIES ) • Urethral suppositories ( BOUGIES ) • Nasal suppositories • Ear suppositories
VAGINAL SUPPOSITORY • They are also called as PESSARIES. • SHAPE : globular, oviform or cone-shaped. • Used occasionally. • Intended for local effects like contraceptives, antiseptics in feminine hygiene
URETHRAL SUPPOSITORY • Also called as BOUGIES . • SHAPE – slender, pencil-shaped. • Intended for anti-bacterial or as a local anesthetic preparative for urethral examination. • Occasionally used.
RECTAL SUPPOSITORY • Intended for local action to relieve constipation, irritation, itching and inflammatory associated to hemorrhoids
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
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
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.
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.
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
IDEAL PROPERTIES OF SUPPOSITORY BASES 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.
Specifications of suppository bases 1- Origin and chemical composition • The source of origin (i.e. entirely natural or synthetic or modified natural). • Physical and chemical incompatibilities with additives (i.e. preservatives, antioxidants and emulsifiers)
Specifications of suppository bases 2- Melting range • Since fats do not have sharp melting point, their melting characteristics are expressed as a range indicating the temperature at which the fat start to melt and the temperature at which it is completely melted.
Specifications of suppository bases 3- Solidification point • This value indicates the time required for base solidification when it is chilled in the mold. • If the interval between the melting range and solidification point is 10ºC or more, the time required for solidification may have to be shortened for a more efficient manufacturing procedure by augmenting refrigeration.
Specifications of suppository bases 4- Saponification value • The number of milligrams of potassium hydroxide required to neutralize the free acids and to saponify the esters contained in 1 gm of fat is an indication of the type of glyceride (mono- or tri-) as well as the amount of glyceride present.
Specifications of suppository bases 5- Iodine value • This value express the number of grams of iodine that react with 100 gm of fat or other unsaturated material. • The possibility of decomposition by moisture, acids, and oxygen (leads to rancidity in fats) increases with high iodine values.
Specifications of suppository bases 6- Water number • The amount of water in grams, which can be incorporated in 100 gm of fat is expressed by this value. • The water number can be increased by addition of surface active agents.
Specifications of suppository bases 7- Acid value • The number of milligrams of potassium hydroxide required to neutralize the free acid in 1 gm of substance is expressed by this value. • Low acid values or complete absence of acid are important for good suppository bases. • Free acids complicate formulation work, because they react with other ingredients and can also cause irritation when in contact with mucous membranes.
Formulation of suppositories • Bases • Anti- oxidants • Emulsifying agents • Hardening agents • Preservatives • Thickening agents • Plasticizers
SUPPOSITORY BASES • Bases :They are of two types • Hydrophilic bases • 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; polyoxyethylenesorbitan fatty acid (tween)
TYPES OF BASES OLEAGINOUS BASES : • Cocoa butter • Cocoa butter substitutes or synthetic fats HYDROPHILIC BASES • Water soluble bases : • Glycerogelatin • Soap Glycerin • Macrogol Bases 2.Water dispersible bases : Emulsifying bases
OLEAGINOUS BASES • Cocoa butter or theobroma oil is naturally occuring triglyceride • Solid fat • Melts at 30 - 35°c • Forms emollient oily liquid in the body cavities and allows drug release
Limitations of cocoa butter • Undergoes rancidification • Undergoes temperature dependent polymorphism • Polymorphs of cocoa butter • Cocoa Butter Slow Heating And Slow Cooling β ( 34-35°c) α 20-22°c β‘ 24-28°c β ( 34-35°c) • Cocoa Butter Over Heating And Rapid Cooling ɼ ( 15-18°c) • Poorly miscible with body fluids , poor water holding capacity • Certain drugs like volatile oils reduce its M.P-minimized by 4% bees wax and 20% spermaciti • Lower contractibility – adhere to moulds • Low solidification – sediments insoluble drug • Disagreeble odor , • Leaks from the body cavities • Melts in warm climates • Leaks from body cavities
SYNTHETIC FATTY BASES Hydrogenated vegetable oils • Ex: coconut oil , palm kernal oil , cottonseed oil, peanut oil , fractionated palm kernal oil • Hydrogenation increases resistance to rancidification and increases chemical inertness
Merits over cocoa butter • Due to saturated nature these bases are less prone to rancidity • Donot exhibit polymorphism on heating • Exhibit good water absorption and emulsifying properties • Small melting range • Solidify rapidly in the mould • Shrink sufficiently making lubrication unnecessary • Melting points don’t effect drug release • Suppositories of these bases – WHITE,SMOOTH, ODORLESS
HYDROPHILIC BASES • Drug release from these bases involves – DISSOLUTION OF BASE • Hydrophilic nature contributes to drug release and absorption • Higher melting points – PREVENTS problems like compounding , handling , storage
Water soluble bases • 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.
GLYCERO-GELATIN SUPPOSITORIES ADV: • Laxative purpose • Vaginal therapy Limitations : • Glycerin is hygroscopic – cause mucosal irritation • Gelatin – incompatibile to drugs like tannic acid,ferric chloride • Preparation of base is time consuming • Tendency to stick to the mould
MACROGOL BASES • These are polyethylene glycols which range from liquids , semisolids ,waxy solids as per molecular weight • Due to their hygroscopic nature PEG Bases dehydrate mucosa to produce irritation • To reduce that discomfort they are dipped in water before insertion • Incorporation of 10-20% water in base also overcomes mucosal irritation and facilitates addition of water soluble bases
Merits • Application in tropical climates • Good solvent properties • They become soft and release medicament slowly for longer period of time • Highly viscous – no leakage of drugs • Suppositories - Attractive , clean , smooth surfaces • Donothydrolyse , rancidify • Donot support microbial growth
Limitations • Complexation of some drugs with macrogols • Formation of brittle and granular suppositories due to crystallization of substances • Incompatible with drugs like tannins , phenol and plastic containers
WATER DISPERSIBLE BASES • Include NON-IONIC SURFACTANTSlike Tween , span • Act as self emulsifying agents in water forming soft , bulky , non irritant emulsions • Promote drug release and drug absorption Satisfy criteria like • Temperature stability • Non toxicity • Non greasy • Good moulding ability • Drug compatibility • Resistance to microbial growth • Increased contact with mucous membrane
Anti-oxidants • They protect the drug and the base from getting degraded due to oxidation. • Examples : • Ethyl or propylgallate • Ascorbic acid and its esters • Hydroquinone • Tocopherols
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 61) • Wool alcohol ,wool fat Hardening agents: • These are included in those formulations where the melting point of the base is decreased by the drug.
These agents bring the melting point to normal. • Examples : macrogols with high molecular weight. Preservatives : They should be included in suppositories which contain water soluble bases to prevent microbial growth. • Examples :methyl paraben , propyl paraben Thickening Agents: They increase the viscosity of molten base and prevent sedimentation of suspended insoluble solids. • Examples: Aluminium monostearate ,collodial silica ,magnesium stearate.
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
PREPARATION METHODS • Suppositories are prepared by four methods:- • HAND MOLDING METHOD • COMPRESSION MOLDING METHOD • POUR MOLDING METHOD • AUTOMATIC MOLDING METHOD.
HAND MOLD SUPPOSITORIES • Advantages:- • Suitable for thermo labile ingredients. • Economical for the manufacture of small number of suppositories. • Disadvantages:- • No uniformity in shape & size of suppository.
