I. INTRODUCTION o Pulverization by Intervention – addition of volatile
substance to gummy materials (ex. camphor + alcohol; I2 Dosage Forms – drug products/preparations containing: crystals + ether) o Active Pharmaceutical Ingredient (API)/ Drug Mixing/Blending o Exipients/Additives/Adjuncts o Trituration – mortar and pestle Drug – any article intended for use in diagnosis, cure, Types of mortar and pestle treatment, mitigation or prophylaxis in man and other animals Glass – smooth non-porous surface; for simple – affects the structure or any function of the body admixture; for chemicals that stain Excipients – inactive ingredients Porcelain – rough inner surface; for comminction o Role: drugs more appealing and efficacious Wedgewood – rougher surface; for crystalline o Use: solubilize, suspend, emulsify, dilute, stabilize, substances preservatives, color, flavor, etc. o Spatulation – use of spatula; not for potent substances Placebo – dosage form that does not contain an API o Sifting – use of sifter; not for potent substances Drug Delivery System – products that allow for uniform o Geometric Dilution – addition of an equal volume of diluent release and targeting of drugs into body to a potent substance placed in a mortar Cosmetics – any substance/preparation intended to be placed o Tumbling – large containers rotated by a motorized process in contact with external parts of human body or with teeth and TYPES OF POWDER mucous membranes of oral cavity with a view exclusively or o Bulk Powders – dispensed in large quantities mainly to cleaning them, perfuming them, correcting body Oral Powders – dissolved/dispersed in a liquid or mixed odors, changing their appearance, protecting them and/or with food before use keeping them in good condition Dentrifices – contain a soap, mild abrasive and Compounding – preparation, mixing, packaging or labeling of anticariogenic agent a drug to prepare an individualized drug treatment for a Dusting Powders – locally applied non-toxic powders that patient have no systemic action REASONS FOR FORMULATING DOSAGE FORMS: appearance, Douche Powders – dissolve in warm water prior to use as palatability, ease of administration, solubility, stability cleansing agent/antiseptic for a body cavity Insufflators – blown into body cavities using an insufflator II. SOLID DOSAGE FORMS Triturations – dilutions of potent powdered drugs (10% A. POWDERS API) o Divided Powders/Chartulae – dispersed in individual doses intimate mixtures of finely divided drugs or chemicals in dry usually in folded papers form which may be used internally or externally TYPES OF POWDER PAPER size: sieve no. o White Bond Paper – opaque paper with no moisture o very coarse – no. 8 resistance o coarse – no. 20 o Glassine Paper – glazed transparent moisture-resistant o moderately coarse – no. 40 paper o fine – no. 60 o Vegetable Parchment – thin, semi-opaque, moisture- o very fine – no. 80 resistant paper Advantages: rapid dispersion of ingredients; flexibility in o Waxed Paper – transparent waterproof paper; suitable for compounding; good stability deliquescent and hygroscopic drugs Disadvantages: inaccuracy of dose; not suitable for dispersing deliquescent and hygroscopic drugs COMPOUNDING: o Trituration – mortar and pestle o Levigation – forming a paste by addition of levigating agent (ex. mineral oil, glycerin)
B. GRANULES Sublingual Tablets – dissolve rapidly under tongue for systemic absorption (ex. Nitroglycerin, ISDN) prepared agglomerates of powders; size: sieve no. 4 to 12; for Lozenges – candies that dissolve slowly in mouth for local tablet formulation: sieve no. 12 to 20 effect (ex. Strepsils® - dicholorobenzyl alcohol + Advantages: flow well compared to powders; less tendency to amylmetacresol) cake or harden; more stable to humidity; more easily wetted TYPES: by liquids Troches – compressed lozenges PREPARATIONS: Pastilles – molded lozenges o Wet Granulation – most common; addition of liquid binder Lollipops – lozenges on sticks o Dry Granulation – for moisture-sensitive and heat labile o Tablets Used to Prepare Solutions materials; use compaction/compression forces Effervescent Tablets – ex. Alka-Setlzer® - antacid + pain o Effervescent Granules – dissolved in water before use in reliever which CO2 gas is released to mask the unpleasant taste of Compounding/Dispensing Tablets – contain a large drug amount of API used by pharmacists in compounding COMPONENTS: multiple dosage units o NaHCO3 Hypodermic Tablets – used by physicians to prepare o Citric acid sticky parenteral solutions o Tartaric acid crumble Molded Tablets/Tablet Triturates PREPARATION: o Dry/Fusion Method – binder is 1 molecule of water in citric acid D. CAPSULES o Wet Method – binder is water + alcohol solid dosage forms in which drug is endosed within either a hard or soft soluble shell usually made of gelatin C. TABLETS o Gelatin – partial hydrolysis of collagen from the skin/bones solid dosage forms which are prepared mainly by compression of animals or molding Types: Advantages: precision and low content variability; low Type A – acid hydrolysis manufacturing cost; easy to package and ship; simple to Type B – base hydrolysis identify; most stable of all oral dosage form; tamper proof Alternative: hydroxypropyl methylcellulose (HPMC) or Disadvantages: some drugs resist compression; some drugs stach that require encapsulation prior to compression Types of Capsules: TYPES OF TABLETS: Hard Gelatin Capsules – dry-filled or two-piece capsules (cap o Tablets for Oral Ingestion and body) Compressed Tablets – formed by compression; some are o made of gelatin, sugar and water + colorant + opacifying scored agent (TiO2) + SO2 [0.15%] (to prevent decomposition of gel) Multiple Compressed Tablets – ex. layered tablets, o contains 12-16% moisture compression coated tablets o stored at 21-25oC/30-35% RH Coated Tablets o capsule sizes: (increase capsule size = decrease capacity) Sugar Coated Tablets – coated with a water soluble Human – No. 5 (smallest) – No. 000 (largest) sucrose-based solution Veterinary – No 10. – No. 12 Film Coated Tablets – coated with a thin layer of Soft Gelatin Capsules – one-piece capsules; contains non- polymer material aqueous liquids (vitamin e, cod liver oil, digoxin), suspensions, Enteric-Coated Tablets – remain intact in stomach and pastes, and dry solids disintegrate in small intestine o made of gelatin, plasticizer (glycerin, sorbitol) and o Tablets Used in the Oral Cavity preservatives against fungi Chewable Tablets – chewed in mouth before swallowing; o contains 6-10% moisture does not contain disintegrant; diluent: mannitol and o no specific sizes xylitol Rapidly/Orally Disintegrating Tablets – liquefy on tongue before swallowing (ex. Resperidone, Ondasetron) Buccal Tablets – dissolve slowly in cheeks/buccal pouch for systemic absorption (ex. Progesterone)
E. ORAL MODIFIED-RELEASE SOLID DOSAGE polymorphism (ȣ - least stable [18oC]; α; β’; β – most stable [34.5oC] FORMS Wecobee ® - from coconut drug release features are based on time, course and locations Witepsol ® - saturated PAs (C12-C18); major: lauric acid Reasons: Glyceryl Monopalmitate o to prolong therapeutic effect to reduce dosing frequency Water-Soluble/Miscible Base o to delay the effect Glycerinated Gelatin – most common base for pessaries Polyethylene Glycol (PEG) o PREPARATIONS: MTC Hand Molding/Rolling/Shaping – oldest and simplest; base is rolled into desired shape by hand Cp Compression Molding – base is forced into molds; problem: air entrapment MEC Pour/Melt Molding – most common; base melted and poured into molds immediate controlled Vaginal Tablets/Inserts – ovoid tablets inserted into the sustained delayed vagina using a plastic inserter; contains antimicrobial agents Implants/Pellets – small, sterile cylinders or devices inserted under the skin for prolonged and continuous absorption Time o Norplant ® - levonorgestel (5 years) onset onset o Leuprolide – prostate cancer (1 year) Types: o Extended-Release – provides a prompt-desired effect III. SEMI-SOLID DOSAGE FORMS3 followed by a gradual release of remaining amount Problem: dose dumping A. OINTMENTS Types: semi-solid dosage forms applied externally on the skin or the Controlled Release – zero order mucous membranes Sustained Release – first order Types: o Delayed-Release – drug release is other than the time of o Medicated – contains activated pharmaceutical ingredients prompt administration (API) o Repeat Actions – contains 2 single doses of a medication (1st o Non-Medicated – used as base dose immediate; 2nd dose delayed) Ointment Bases: o Targeted Release – drug release is isolated in a specific body o Oleaginous/Hydrocarbon Base – greasy, anhydrous, region/tissue absorption and action emollient, occlusive, non-water washable Petrolatum/Yellow Petrolatum/Petroleum Jelly (Vaseline®) – purified mixture of semisolid hydrocarbon D. PHARMACEUTICAL INSERTS from petroleum Suppositories – solid masses inserted into body cavities in White Petrolatum – decolorized which they will melt at body temperature or dissolve into Yellow Wax/Beeswax – wax obtained from the aqueous secretions of body orfice honeycomb of Apis mellifera o Types: Rectal; Vaginal (Pessaries); Urethral (Bougies) – ex. White Wax – bleached Alprostadil (for erectile dysfunction) Yellow/Simple Ointment – yellow petrolatum + yellow FEATURES RECTAL VAGINAL URETHRAL wax SHAPE Bullet Globular Pencil-like Torpedo Ovoid White Ointment – white petrolatum + white wax Cone o Absorption Base – greasy, emollient, occlusive, non-water WEIGHT Adult: 2g 5g Male: 4g washable; can absorb small amounts of water w/o Pedia: 1g Female: 2g SIZE Adult: 32mm Varies Male: 140mm Hydrophilic Petrolatum (Aquaphor®) – petrolatum + Pedia: 16mm Female: 70mm cholesterol (emulsifying agent) + beeswax + stearyl INTENDED USE Both Local Local alcohol o SUPPOSITORY BASES Anhydrous Lanolin/Woolfat – wax-like substance from Oleaginous Base the wool of Ovis aries (sheep) containing 0.25% moisture Cocoa Butter – most common base for rectal *Hydrous Lanolin – 25% moisture; Modified Lanolin – suppository; solid at 32oC, melts at 34-35oC; exhibits without free lanolin alcohols and excess detergents
o Water-Removable Base – o/w; water-washable; non- IV. TRANSDERMAL DRUG DELIVERY SYSTEM occlusive; non-greasy; can be diluted with large amounts of controlled release DDS or patches which allow the passage of water drugs from the skin to the systemic circulation Hydrophilic Ointment PARTS OF TDDS: o Water-Soluble Base – lipid-free; greaseless; water- o Occlusive Backing Layer – prevents water loss and drug loss washable; non-occlusive; for incorporation of solid materials o Drug Matrix System – stores API Polyethylene Glycol (PEG) Ointment – MW < 600 o Adhesive Layer – ensures continuous drug absorption liquids; MW > 100 wax-like solids; MW 600-1000 o Release Liner – removed before use to enable drug release semisolids EXAMPLES: o Scopolamine (Transderm Sccp®) – 1st TDDS developed; for B. CREAMS motion sickness semi-solid preparations containing APIs dissolved or dispersed o Nitroglycerin – angina in w/o or o/w emulsion or water-washable base; preferred: o Clonidine – 1st TDDS for hypertension ease of spreadability o Fentanyl – opioid analgesic o Vanishing Creams – o/w base; large % water – ex. glycerin, o Estradiol and Testosterone – hormone replacement therapy propylene glycol – + stearic acid o Cold Cream/Petrolatum Rose Water Ointment – w/o base; V. LIQUID DOSAGE FORMS SINGLE PHASE mineral oil less rancid; white wax; spermaceti (cetyl Solutions – liquid preparations containing one or more esters wax) + Na borate substances dissolved in a suitable solvent Advantages: completely homogenous dose; immediate C. GELS availability for absorption; flexible dispersion systems consisting of small inorganic particles or Disadvantages: degrade more rapidly; interact with other large organic molecules dispersed throughout a liquid vehicle, component; bulky rendered jelly-like by addition of a gelling agent; thixotropy – DESCRIPTIVE TERMS PARTS OF SOLVENT REQUIRED FOR reversible gel-sol formation 1 PART OF SOLUTE Very Soluble <1 Freely Soluble 1-10 D. PASTES Soluble 10-30 semi-solid preparations applied on skin and contain a large Sparingly Soluble 30-100 proportion of solid material (≥25%) and therefore stiffer than Slightly Soluble 100-1,000 ointments Very Slightly Soluble 1,000-10,000 Insoluble >10,000 Use: to prolong contact of drug Water Official Types: Zinc Oxide Paste (ZnO) – treatment of diaper rash o Purified Water – distillation; reverse osmosis; ion exchange o Water for Injection – purified water that is pyrogen-free E. PLASTERS o Sterile Water for Injection – water for injection that is solid or semisolid adhesive masses spread on a backing of sterilized paper, fabric, moleskin or plastic o Bacteriostatic Water for Injection – sterile water for Use: to prolong the contact of drug and affords protection injection with antimicrobial agent (benzyl alcohol); not for Salicylic Acid Plaster – keratolytic (10-40% salicylic acid) neonates o Sterile Water for Inhalation F. GLYCEROGELATIN o Sterile Water for Irrigation plastic masses applied on skin with a fine brush contains: 40% glycerin, 35% water, 15% gelatin, 10% AI A. AQUEOUS SOLUTIONS Zinc Gelatin Boot – treatment of varicose ulcers Aromatic Water/Medicated Waters – clear, saturated aqueous solutions of volatile oils or other aromatic substances; o Use: flavored/perfumed vehicles G. POULTICES/CATAPLASM o Preparations: soft, moist masses of meal, herbs, seeds, etc.; applied hot in a Distillation – not economical; only method for: Strong cloth Rose Water, Orange Flower Water Use: to localize infectious materials and counterirritant Simple Solution – with or without dispersant (ex. talc) Kaolin Poultice – treatment for boils and anti-inflammatory o Problem: Salting out – insoluble layer at top