Traditional Capsules

Traditional capsules formulations Consists of a 2 piece hard colloidal gelatin shell, with a powderise blend. typical formulation would be- Active Diluent Glidant Lubri washstandt Wetting agent Capsules have advantages as oral venereal disease forms Easy to administer, simpler formulations (Vs tablets-fewer stability problems) Taste/ perfume masking Potentially good bioavailability Liquid filled capsules -Advantages 1. Dose Uniformity In a powder capsule for cockeyed drug choice the problems be achieving homogenous mix at the required scale of scrutiny. To overcome this problem we could formulate as a solution 100% homogenous.Filling liquefiables also avoids problems of poor powder flow if this occurs during choice, can lead to variation of fill weight. (with a 1% possible) . 2. Patient safety compliance/consumer preference Softgel capsule shel soft/flexlble popular dosage form, due to Ease of swallowing Absence of taste Convenience (portable, robust) Soft gels capsules can be formulated to be taken In different ways tender or lozenges Twist-offs (with a tag allows access to contents) 3. Increased Bioavailability Dissolution of drug from secure state (I. e formulated as an ordinary tab/cap) can be rate limiting step.This often true for non-polar drugs. But In llquld fill cap, drug Is In a form from which It can be absent-minded rapidly. Drug being In solution has additional advantage (I. e Vs tablet, fro low solublllty drug) Reduces varlablllty of drug plasma takes (between patients) 4. Safety Powder processing of very potent or cytoxlc drug hazardous dust contamination avoided by solution. 5. Olly/low laming point drugs Dlffllcult to make Into normal tab/cap (drug could partly melt during compression) 6. Product stablllty Drug can be protected against 02/H20 by using llpld vehicle and soft gel shell.Considerations for Capsule shell Having llquld In direct fill with the shell -more potential for formulation -pack Interaction, particularly affect ing Integrity. Therefore, any trace of water can non be utilize because water dissolves gelatin hence wont work. Llqulds can be filled Into Dotn sort ana nara cap- out OITTerent conslaeratlons apply. cant necessarlly Till same formulation into both types, consume to think about composition of the shell itself (gelatin) jelly for Hard Capsules of import problem Liquid fill hard gel caps is Residual moisture loss. rom the shell into the formulation Hydrogels require 13% to 6% level of moisture, to retain strength. Hence hygroscopic solvents cannot be used as excipients in liquid filled caps since they might take up some water. E. g ethanol, liquid PEG, glycerol, PG. (all these cannot be used for hard capsule) During preformulations studies, we have to check that excipients are compatible with shell. Excipients that can be used for hard capsule Lipophilic liquids/ fishing tackle solids e. g arachis, castor, olive oils. Also some surfactants & emulsifiers. As an alternative, could c onsider HPMC (hydroxypropyl methylcellulose) caps.Residual water not so important for integrity of shell, so wider range of olvents may be possible. Gelatin for soft capsules Formulation of soft gel caps themselves are different to hardgel . Typically the gelatin plus Plasticiser ( to give flexibility). Often 20-30% Glycerol is frequently used Water lower residual level than hardcaps, 5-8% Colourant /opacifier Lower water level needed for the soft caps means hydrophilic solvents e. g. PEG 400can be used contrasted for hard gels. (but need to be aware of migration into shell) Manufacture of Hardgel Caps In brief, Formulation is pumped into bottom half of shell, then cap is replaced.Issues for manu. Hardgel caps Formulation viscosity (liquid & semi solid possible) Temperature of filling Sealing of capsule shell afterwards NB Therefore need to consider physical aspects of formulation, as well as filling equipment available. Rheological Considerations Simplest formulation is a solutio n in which active dissolves, at room temp. Very precise control of filling possible. In-soluble active If active is not soluble, could consider using elevated temperatures, up to 70Deg. Celcius. (Above this could damage the shell) But when the temperature falls again, inside the shell drug would re-precipitate at RT.As a consequence resulting particle sizing will be important (bioavailability). Another problem Recrystallized/suspended drug inside capsule shell wil have a potential to cake re normal suspension, could get crystal growth. t Is posslDle to Till a suspenslon out tnen anotner proDlem to solve May oe a to keep homogenous, during filling. 2 Alternatives for insoluble drugs 1 . Thixotrpic gel Undergoes shear thinning during mixing/filling. so then enough to but gel resets in capsule Typical formulation- Lipophilic solvent (oil) *gel-former (e. g. silicon dioxide).Silicon ioxide completely forms a gel in a lipophilic environment. 2. Thermosoftened system Formulation is a liq uid or suspension at (elevated) filling temperature, but solid or semi solid at RT. Typically based on a high molecular PEG, eg PEG 10,000 (soft but solid) If drug crystallises, will need to consider resulting particle size as previously. Manu. Of Hardgell caps contd a)Filling- Hardgell caps On a development (small) scale, can use a syringe. Large-scale machines use volumetric pumps- hopper and bird of night can be heated. Up to 100,000 caps/hr possible.