Pharmaceutical Preparations and Drug Forms - Dosage Forms PDF

PHARMACEUTIC AL PREPARATIONS AND DRUG FORMS Abdel-Fattah M. Ali prof. of Vet. pharmacology  VETERINARY DOSAGE FORMS Veterinary dosage forms are essentially pharmaceutical drugs product in the form in which they are marketed for use typically involve a mixture of active drug and n...

PHARMACEUTIC AL PREPARATIONS AND DRUG FORMS Abdel-Fattah M. Ali prof. of Vet. pharmacology  VETERINARY DOSAGE FORMS Veterinary dosage forms are essentially pharmaceutical drugs product in the form in which they are marketed for use typically involve a mixture of active drug and non-drug component (excipients). Dosage forms are the means through which drugs are delivered in the body towards its site of action. T h e y are the final product containing drugs that is administered to the patients. Dosage forms includes active drug and pharmaceutical excipients. 3 Drug (active pharmaceutical ingredient - API) Any substance intended to be used in diagnosis, treatment or prevention of diseases. Or An exogenous substance that when absorbed into the body of a living organism, alters normal bodily function Drug (active pharmaceutical ingredient - API) Any substance intended to be used in diagnosis, treatment or prevention of diseases. Excipients (inactive pharmaceutical ingredient ) Technological, biopharmaceutical and/or stability reasons. Diluents/fillers binders, lubricants, desintegrants coatings, preservants and stabilizers colorants and flavorings Reasons for the need for dosage forms 1. To protect the drug substance from destructive influences of atmospheric oxygen 2. To protect the drug from the destructive influence of gastric acid after oral administration 3. To conceal the bitter, salty, or offensive taste or odor of a drug substance. 4. To provide liquid preparations of substance that are insoluble in desired vehicle 5. To provide for insertion of a drug into one of the body’s orifices 6. To provide optimal drug action from topical administration sites, etc. 6  The dose: is the amount of drug taken at one time. It can be expressed as the weight of drug (e.g. 250 mg), volume of drug solution (e.g. 10 mL, 2 drops), the number of dosage forms (e.g. 1 capsule, 1 suppository) or some other quantity (e.g. 2 puffs). The dosage regimen: is the frequency at which the drug doses are given. Examples: include 2.5 mL twice a day, one tablet three times a day, one injection every four weeks.  The total daily dose: is calculated from the dose and the number of times per day the dose is taken. The strength: is the amount of drug in the dosage form or a unit of the dosage form E.X: 500 mg capsule 250 mg/5 mL suspension). DOSAGE FORMS 9 Classification: Dosage forms are classified according to Route of drug administration into: I. Enteral II. Parenteral III. Inhalation IV. Topical 1 1 CLASSIFICATION OF DOSAGE FORMS 12  1.Unit solid: 1.Monophasic liquid: - Inhaler syrup o tablets - aerosols Solution o capsules 2.Biphasic liquid:- 2.Bulk dosage form: emulsion o powder suspension o Dusting powder - Cream - Paste - Gel 1 - suppositories 3  Types of Dosage Forms  Tablets  Boluses  Capsules  Drinking Water Medication  Parenteral Dosage forms  Oral Pastes and Gel  Drenches and Tubing Products  Topical Dosage Forms 14  Feed Additives 15  TABLETS ❑ Tablets are solid oral dosage forms of compressed powders or granules intended for oral administration. ❑ They are unit dosage form of medication containing specific amount of drug. ❑ They are prepared with the aid of pharmaceutical excipients. ❑ They vary in size, shape, weight, hardness, thickness, disintegration and dissolution. ❑ They are the most widely used and convenient dosage form in human but not in animals.  TABLETS Solid dosage form like compressed tablet is most common in case of humans. They are less popular in animals because administration is uncertain. Why the administration is uncertain…??? “It is uncertain because one cannot be sure the tablet is swallowed, spit out, or drop from mouth after administration.” 17  TABLETS ❑ Typically the tablet are chewed by the animals but due to the undesirable taste of certain drug the animals can spit out that tablet from the mouth, this will result in loss of dosage form. ❑ To avoid this, the flavoring agents, sweeteners can be added to the formulation. 18  TABLETS Tablets are classified according to their form into: Compressed tablet: prepared by compression. They are lenticular in shape (like lentil seed). Triturated tablet: prepared by mixing the drug with a suitable diluent as lactose and the mixture is moisted with alcohol and the mass is pressed into circular holes in a suitable plate and are allowed to dry flat and disc shaped.  TABLETS Types Special Tablets Compressed Tablets Sub-lingual tablets Dispersible tablets Buccal tablets C h e w a b l e tablets Va g i n a l t a b l e t s F i l m coated tablets Rectal tablets E n t e r i c coated tablets Effervescent tablets Molded tablets I m m e d i a t e release tablets ❖ H y p o d e r mi c t a b l e t s S u s t a i n e d release tablets ❖ Dispensing tablets  TABLETS Tablets are either: ❑ Coated or non-coated: Coated tablets are either covered sugar (sugar coated tablet) to avoid tasting the drug; or covered with acid resistant covering (enteric coated tablet) as “salol” to allow the tablet to pass unchanged through the stomach but is dissolved in the alkaline media of the intestine. They are used to avoid the irritant effect of the drug on the stomach. ❑ Tablet may be divided or non-divided: to facilitate administration of the dose. ❑ Tablet Size: very small size for sublingual administration large size reaches 2 grams as effervescent tablet. Manufacture Process for Tablets Blending and Capsules Wet Granulation Dry Milling Compression Coating Labeling Packing  PILLS ❑ Pill (Bilula): is a drug preparation mixed with stickily substance and molded into spherical form to be easily swallowed. as a rule pills should not weigh more than 0.3 g. Pills are coated with sugar if the drugs are liable to change on exposure to air or of volatile, bitter or nauseous nature it is used for small animals. 23  CAPSULES Capsule: They are unit solid dosage forms consisting of gelatin shell that breaks open after the capsule has been swallowed and releasing the drug. Capsule-shaped tablets are commonly referred to as caplets. Types: 1. Hard gelatin 2. Soft gelatin 24  CAPSULES 1. Hard gelatin Capsules ❑ manufactured in two pieces that fit together and hold the drug, either in powdered or granular form. ❑ made up of gelatin, sugar and water. ❑ The capsule shell contains low moisture content. They are hard and cylindrical in shape. They contain powders, granules or pellets inside the capsule. 25  CAPSULES Parts of Capsule: ❖ C a p s u l e body ❖ Cap 26  CAPSULES 2) soft gelatin shell ❑ manufactured in one piece with drug usually in liquid form inside the shell, e.g. fat-soluble vitamins A and E); ❑ made up of gelatin, water, glycerin or sorbitol. It contains high moisture than hard gelatin capsule. ❑ used for the filing of liquid or semisolid preparations. They are soft and vary in shape like round, oval, oblong, etc. 27  Cachets ❑ Cachets are moulded from rice paper, a material made by pouring a mixture of rice flour and water between two hot polished revolving cylinders. water evaporates and sheet of wafer is formed. ❑ These are used to mask the nauseous or disagreeable powders in tasteless form for administration. e.g.: Isoniazid cachets, sodium amino salicylate cachets, etc. 28  Cachets Enclosure in cachets provides a means of administering nauseous or disagreeable powders in a tasteless form. There are two kinds; 'wet seal', so called because water is used to seal them, and 'dry seal'. The wet seal type consists of two halves, both alike, convex in shape and having a broad flange that is used for sealing. The dry seal type has a shallow cylindrical base and a slightly larger, slip over cap. Both are made in variety of sizes holding from 0.2 to 2 g of a powder of medium density. They are softened by immersion in water for a few seconds and then taken with a drought of water. 29  BOLUS The bolus is a very large tablet that is intended to be retained in the rumen. A slow dissolution process and ruminal retention provides an opportunity to achieve prolonged systemic drug exposure. A special tablet called a “bolus” is commonly used these large dosage. A bolus is nothing more than a very large tablet , which can range from 3 to 16 g or more. Bolus (Ball): is an elongated cylindrical preparation about 5-7 cm in length, 2 cm in diameter and should weigh 30-45g used for large animals (cattle, sheep & goat). They are made from effective ingredient with liquorice 30 and treacle as a vehicle.  POWDER Powder (pulvis): is a solid drug in finely powdered form ❖ may be simple (i.e. contains one drug only e.g. sulphonamide powder). ❖ or compound (combination of solid drug) ❖ Powder may be used externally or internally. ❖ when used externally they are applied by dusting or insufflation and dispensed in boxes, tins or envelops. ❖ When used internally they are dispensed as such in cachets, capsules or sachets. 31  POWDER sterilized powder such as hormones or antibiotics are dispensed in sealed ampoules or vials away from their solvent to extended their expiry. ❖ Another type of powder is the effervescent powder which contain an effervescent base as bicarbonate or tartaric of citric acid and not react with each other except in presence of water as they effervesce to decrease their unpleasant taste. 32  Drinking water Medications ❑ A common form of medicating animals for herd or flock health is through the drinking water. The medications are formulated as: (a) Dry powders for reconstitution into liquid concentrates to be added to the drinking water or to be added directly to the drinking water or, (b) Concentrated solutions, which are dispensed directly in drinking water or injected into the drinking water through medication proportioners incorporated into watering lines. The advantage of medicating through drinking water versus feed is that sick or unhealthy animals will continue to drink water whereas 33 they may not eat.  Drinking water Medications ❑ Oral liquids are one of the easier dosage forms ❑ The main challenges are finding a vehicle that result in adequate chemical stability while achieving a solution. The first vehicle choice will be water. ❑ It needs Good understandings of the pH and temperature effect on solubility to ensure no precipitation of the marketed product when exposed to abrupt changes in temperature and pH. 34  Drinking water Medications ❑ Whether a product is formulated as a dry powder, dispensing tablet, or liquid concentrate, The following must be considered: ❑ Tablet or granule hardness, buffer capacity, pH, and total dissolved solids all play a role in the solubility rate and availability of the drug substance, as well as its stability ❑ The drug stability in the drinking water should be adequate for the storage length of time listed on the label. ❑ Consideration also has to be given when formulating a liquid concentrate using solvents other than water due to the possibility of precipitation or recrystallization of the drug when diluted with water. ❑ All of the above factors make drinking water formulation is challenging task. 35  Parenteral dosage forms Solution: Clear mixture of two or more component to form a single homogenous phase ( molecules level) “Water for injection” is the most widely used solvent for parenteral formulations. Suspension: Insoluble biphasic solid particles dispersed or suspended in liquid medium (shake before use) Emulsion: Heterogeneous dispersion of two immiscible liquid in another it relies on an emulsifying agent for stability. Parenteral emulsions are rare because it is seldom necessary to achieve an emulsion for drug 36 administration.  Parenteral dosage forms  Dry powder: Reconstituted as a solution or suspension immediately prior to injection The principal advantage of this dosage form is that it overcomes the problem of instability in solution Injection: is a sterilized preparation of drugs in the form of solution or suspension intended for injection. They are dispensed in ampoules or vials. Ampoules is a sealed glass contained one dose of a drug in the form of sterile solution for injection. while vial is a bottle of small or large size closed with rubber cap contain sterile solution for single or multiple doses. Solution may be aqueous or oily. They also may contain sterilized powder and a solvent added only before use to 37 keep its potency and prolong its expiry date.  Intra-mammary InfusIon Intra mammary infusion product are available for lactating and non-lactating cow. Lactating cow intra mammary infusion should demonstrate fast and even distribution of the drug and a low degree of binding to under tissue. These properties result in lower concentration of drug residue in milk. 38 Intra-vaginal Delivery system Intra-vaginal system includes polyurethane sponges containing synthetic progestin; capable of delivering multi drug at a predefined time, either pulsed or continuous fashion and a biodegradable insert called PCL (polyepsilon- caprolactone) or polyhydroxybutyrate-valerate (PHBV) intra-vaginal insert. Polyurethane sponge containing progestin 39  IMPLANT Implant or hypodermic tablet: is a minute cylindrical or disc shaped solid preparation, usually contain certain steroids as hormones, inserted under the skin to be absorbed slowly to prolong their action e.g. stilbosterol implant. The majority of implants used in veterinary medicines are compressed tablet or dispersed matrix system in which the drug is uniformly dispersed in non- degradable polymer. 40 A) Gaseous forms of drugs include: Gases: e.g. No2 , Cyclopropane, O2 , CO2 , and ether mixture for anaesthesia. Inhalent: i.e. a volatile drug dispensed in an inhaler (spray) for the treatment of conditions of the respiratory tract e.g. salbutamol and ephedirine spray in bronchial asthma. 41  B) Liquid forms of drugs include: Aqua: is the watery solution of volatile substances e.g. aqua chloroformi, aqua anisi, aqua, peppermint. It may be distillated (aqua distillata). It is used as a solvent or a vehicle for hanging drugs. Mixtures (Suspensions): is a combination of drugs in a liquid form for internal use as haematinic mixture and white mixture. 42  B) Liquid forms of drugs include: Emulsions: is a preparation of two immiscible liquids one of them is broken up into minute globules each surrounded by a film of an emulsifying agent added to them (as gum acacia, gum tragacanth, etc) and suspended throughout the other liquid. Medicines are prepared in the form of emulsion to…… obscure the nauseous and greasy character of the oil as cod liver oil emulsion and caster oil emulsion. 43  B) Liquid forms of drugs include: Syrup: Concentrated aqueous solution of sugar is either simple or medicated syrups. Simple syrup is a watery solution of sugar commonly used as flavoring agent or aqueous vehicle while medicated syrup contain active drug and can be prescribed alone or together with other drugs as syrup tolu and syrup ipecac. Elixir: A flavored fluid containing alcohol and syrup as Elixir ferri.(aromatic) Elixir is less sweet and less viscous than syrup 44  Infusion Decoction Infusion: is a preparation Decoction: is a made by pouring hot or cold preparation similar to that water or dilute alcohol upon of infusion except that they powdered plant then shacked are prepared by boiling the from time to time and strained vegetable in water usually after half hour. It must be for ten minuets, then freshly prepared as infusion strained as decoction of senna. quassia or tea. ‫استخالص بالغليان‬ 45  B)Extract Liquid forms of drugs include: ❑ Extract: is a preparation obtained by treating or macerating the ‫استخالص بالمذيبات‬ crude plant with a suitable solvent and then evaporation of the solvent to obtain the extract. ❑ According to the degree of evaporation of the solvent the extract may be fluid extract or solid extract. ❑ In addition, according to the solvent used the extracts are named as alcoholic extract, chloroformic extract, etherial extract, and 46 aquous extract.  B) Liquid forms of drugs include: Tincture Tincture: is an alcoholic solution of non-volatile active principles made by maceration or percolation of the plant. Tinctures are much weaker than extract and must not be stronger than 50%. Spirit (essence): is an alcoholic solution of a volatile substance as chloroform sprit and aromatic spirit of ammonia. 47  B) Liquid forms of drugs include: Collyrium (Eye lotion): o is a weak watery solution of drugs applied by a piece of cotton as washes for the eye o It mainly contains antiseptic or astringent drugs. Ex: boric acid eye lotion Gutta ophthalmica (Eye drop): ❑ is a watery solution of drugs to be instilled into the eye by eye dropper as pilocarpine and atropine eye drops. ❑ It may contain antibiotics, astringents, anaesthetics or drugs of different pharmacological actions. 48 ❑ Fomentations: is a piece of cotton soaked in water or solution of a certain drugs to be applied on an inflammed part of the skin to lessen tension and relieve pain. Fomentations may be hot or cold, medicated or non medicated e.g. hot and cold water fomenta, and lead subacetate fomentations. ❑ Lotion: is a watery preparation, which is applied externally on the affected part of the skin without friction to produce a soothing action as calamine lotion Liniment: is a liquid or viscid preparation that is rubbed onto the skin to produce a rubeficient or anodyne effect. Liniments have usually an oily, alcohol or soapy vehicle in which drugs are dissolved as camphor liniment and turpentine liniment.  ❑Enema: is a liquid preparation intended to be administered per rectum e.g. Nembutal anaesthesia in dogs. Poultice: is a preparation of hot pasty material applied to any part of the body increase local circulation or alleviate pain e.g. Kaolin poultice, linseed poultice.  Ointment: is a semi-solid Oculentum (Eye): is an preparation containing ointment containing drugs drugs mixed with a fatty intended to act upon the substance as vaseline, eye such as penicillin eye lanoline, lard, etc to permit ointment, yellow oxide of its application on the skin mercury ointment, such as sulphur ointment, atropine sulphate eye zinc oxide ointment. ointment.  Suppository Pessary: is a conical or torpido- is a globular or oviform shaped solid preparation shaped solid preparation to be to be administered per inserted into the vagina. They rectum. Suppositories are are made with a vehicle of made of vehicle theobromine oil, which has a theobromine oil (butter of melting point slightly below the body temperature, so that, after cacao) to facilities its insertion into the vagina melting by the body become melting and the drug is temperature and the liberated and come in contact release of active drug with the vaginal mucosa.  ORAL PASTE & GEL Pastes and gels are semi-solid masses that can be administered from a flexible tube, syringe, package or other specialized dosing devices. Three types of vehicles are used to formulate a paste or gel. Oil base Aqueous Organic base base 53  DRENCH & TUBING PRODUCT Administration of the drug to animal by pouring the liquid medication down an animal’s throat is called “Drenching”. Drenches are dispensed via the syringe or drenching gun. Anti parasite medication Ivermectin Drench 34 DRENCH & TUBING PRODUCT LIQUID DRENCH GUN POWDER DRENCH GUN 55  T U B I N G P RO D U C T Horses are administered certain medication by running the lubricated tube up through the nostrils and down into the stomach. A funnel is attached to the tube is held above the horse head and the liquid medication is poured down the tube. This is called “tubing”. 56 T O P I C A L Dosage forms Pore on Application Dust Dips Bags 57  pore – on/spot – on A p p l i c a t i o n ❖ These products are generally used against ectoparasites. They act as neurotoxins. ❖ In cattle the spot-on are mainly used to control of grabs and lice. Hence they have broad- spectrum antihelmintic activity. These formulations contain organophosphorous insecticides or antihelmintic dissolved in Organic solvent. 58  Dust b a g s Cattles are treated with insecticides powder through use of device called dust bag. Dosing is accomplished by the animal brushing against the bag. The bag has inner porous storage bag containing the insecticide dust formulation. 59  DIPS Dips are use for controlling the ectoparasites in economic animals. Dip formulation contains the drug diluted in a large bath. This bath must be long, wide, and deep enough to deep the animal. 60  F e e d addiTives Feed additive are preparations used in veterinary medicine to deliver the API via the water or food given to the animals. They may be either solid or liquid and sometimes also called as premix. 61 62