Solid Oral Dosage Forms 4 Flashcards
Types of excipient: tablets and capsules
Diluent/filler- to increase size of tablet or fill a capsule shell, to help form compacts or plugs
Binder- use to form granules, either dry or in solution
Disintegrant
Lubricant
Glidant
Wetting agent and stabilisers, colourants and flavours
Diluents: sugars
Good properties, water soluble
Lactose- most commonly used, available in a variety of forms- crystalline and amorphous, spray dried forms used for direct compression
Several sugars/sugar alcohols are used for their taste properties e.g. sucrose, glucose, mannitol and sorbitol
Used in chewable tablets and lozenges
Diluents: starches
Variety of plant sources, mainly for capsules, advantage low cost e.g. maize, potato, rice and local plants
Modified starches used in both tablets and capsules- pregelatinised, better flow properties, starch 1500, physically processed maize starch to improve flow
Diluents: inorganics
Calcium phosphate- dicalcium phosphate dehydrate and anhydrous, insoluble but hydrophilic, readily wetted; tribasic calcium phosphate
Calcium carbonate
Both used as a calcium source in nutraceuticals
Diluents: organics
Cellulose
Microcrystalline cellulose
Powdered (microfine) cellulose
Both have good compaction properties, large change in volume with compression force
Binders
Adhesive materials that hold the granules together
Wet binders- typically aqueous preparation, sometimes added to dry mix and then wetted during granulation
Dry binders- material with good compaction properties added to formulation to improve the compact strength, celluloses
Wet binders
Povidone Cellulose derivatives Gelatin Maltitol, maltodextrin Starch paste Polyethylene glycol Water principal solvent, if cannot be used then replaced with ethanol or isopropanol
Dry binders
Materials that deform plastically and fill voids in tablet mass e.g. microcrystalline cellulose
Disintegrants
Break tablets apart and disrupt powder plug in capsules
Standard Disintegrants: starch, maize, potato, do not work in hard capsules
Super Disintegrants: sodium starch glycolate, crospovidone, croscarmellose sodium
Lubricants
Stop materials adhering to moving metal parts on tabletting and capsule filling machines
Magnesium stearate- most used excipient in SODF
Sodium stearyl fumarate
Stearic acid
Polyethylene glycol
How do tablet lubricants work?
Boundary lubricants- form films at surface of die wall and tablet e.g. magnesium stearate
Stearic acid- melts to form a boundary layer
Anti-adherents
Problem with sticking on faces of tablet punches particularly with embossed punches- fault called picking
Magnesium stearate has a secondary role in preventing sticking
Talc and starches are also used
Glidants
Powders that coat other particles and reduce inter-particulate forces improving flow of the mass
Colloidal silicon dioxide
Talc
Glidants and lubricants
Both act on the surface of particles
If not properly dispersed, do not function
A minimum optimum concentration gives maximum effect and if exceeded adverse effects occur
Concentration to use related to size of surface to be covered
Wetting agents
Added to improve wetting of hydrophobic actives
Sodium lauryl sulphate
Polysorbate 80
Stabilisers, flavours and colourants
Moisture scavengers- colloidal silicon dioxide
Antioxidants
Flavours- used for taste masking of bitter active
Colourants- soluble dyes and insoluble pigments
What is colour?
Requires light source, object, observer, eye or instrument, matching colour by mixing primary colours
Pharmaceutical colourants
Dyes- water soluble, azo, non-azo
Pigments- water insoluble, titanium dioxide, iron oxides, lake form of soluble dyes
Iron oxide pigments
Restrictions in USA- amount used as a colourant must not exceed 5mg of elemental iron per day
Iron oxide and absorption of iron- solubility in artificial gastric juice after 4 hours
What factors influence tablet and capsule formulation?
Size of dose
API properties- compactability, fluidity, solubility, stability
Influence of API dose
Low dose (<25mg): most of tablet or capsule formulation will be excipient, challenge is content uniformity High dose (>250mg): most of tablet or capsule will be API, challenge is compactability and fluidity API solubility important for both, governs selection of excipient
Effervescent tablets
Disintegration by release of gas, carbon dioxide
Reaction between carbonate or bicarbonate and weak acid, citric or tartaric
Prepared by direct compression or by:
Wet fusion: citric acid moistened and added to sodium bicarbonate and granulated, granules dired at 70c
Heat fusion: dry powders blended with citric acid monohydrate and heated to produce granules
Chewable tablets
mechanical disintegration in the mouth
No disintegrant in the formulation
Diluents chosen for their sensory properties
Flavours added to improve taste
Buccal/sublingual tablets
Standard tablets, small size- formulated for fast disintegration
Designed for absorption in buccal cavity achieve rapid action or to avoid first pass metabolism
Sublingual, placed under the tongue
Buccal, placed in side of cheek
Orally disintegrating tablets
Disintegrate in <10 seconds, equivalent to standard immediate release tablets
Designed for aiding compliance of patients who have difficulty in swallowing standard tablets and capsules
Active people who have no access to water for swallowing standard SODF
Formulation: many patented processes, proprietary information
Types of orally disintegrating tablets
Standard tablets
Compression moulded tablets
Freeze-dried tablets
Extra challenges in formulation- taste masking , coating of powder particles, using effervsecence
Orally disintegrating tablets compressed tablet formulation
Rapidly soluble compounds- sucrose, amorphous, mannitol, lactose, amorphous or partly amorphous
Super Disintegrants- up to 10% w/w
Moderate compression forces- achieve high porosity with adequate hardness and friability
Freeze dried tablets
Solution made and dispensed into pre-formed blisters, passed through a cryogenic freezing process that control ice crystal size, hence tablet porosity
Frozen blisters transferred to large freeze driers
Finally open blisters have lids added and heat sealed
