Capsules Flashcards
Capsule
Solid dosage form in which the drug is enclosed within either hard of soft soluble shell
Advantages of Capsules
Mask bitter and unpleasant taste Increased bioavailability Easy to formulate Protection to drug Easy to swall and admin Suitable for delivering liquids, semisolids, and solid drugs Extemporaneous compound is easy Adjustable to individual dosages
Disadvantages of Capsules
Cannot be dispensed
Not suitable for highly soluble salts –> irritate the stomach
Not suitable for highly efflorescent (soften) or deliquescent (brittle) materials
Not suitable for children
Shell quality
Capsule filling is slower than tablet press
Gelatin capsule
Glycine and alanine + other a.a.
Hydrolysis of collagen
- Combo of type A and B is the best
Type A Gelatin
Produced by acid hydrolysis and is mainly manufactured from pork skin
- Plasticity and clarity
Type B Gelatin
Produced by alkaline hydrolysis and is obtained from animal bones
- Firmness
Colorants
Soluble synthetic dyes and insoluble pigments
- Product ID and patient compliance
Opaquing agents
Titanium dioxide
Provide protection against light
Preservatives
Parabens are used
- Water controlls viscosity
Steps to make a hard gelatin capsule shell
Step 1/2: Mix gelatin and water in melting system and transfer to feed tanks
Step 3: Dyes, opacifiers and water are added
Step 4: Gelatin is fed in dipper sections and capsules are molded onto pin bars dipping
Step 5: Pin bars then rise to the upper deck allowing setting
Step 6: Pin bars are passed through a drying system
Step 7: Monitor humidity, temp and gelatin viscosity
Step 8/9: Capsule halves are stripped from the pin
Step 10: Trimmed
Step 11: Bodies are joined
Step 12/13: Packed and monitored
Step 14/15: Visual inspection and imprinted; ready to be sterilized
Successful filling requires?
Lubricity
Compactibility
Flowability
Fillers
Increase the bulk of the formulation
- Starch, lactose, dicalcium phosphate
Glidants
Improve flowability
Coat powder particles
Fill surface irregularities and reduce the roughness, reduce attractive forces
Modify electrostatic charges
Act as moisture scavengers
Serve as ball bearing between host
- Colloidal silicas, talc, magnesium stearate
Lubricants
Help ejects pluds
Reduce filming on pistons and adhesion of powders to metal surfaces
Reduce friction
Increase hydrophobic lubes, retard drug release
- Magnesium stearate, stearic acid
Surfactants
Increase the wetting of powder mass and enhance dissolution
- Sodium lauryl sulfate, sodium docusate
Hydrophilization
Hydrophilic polymers increase the wettability of poorly soluble drugs
- Metylcellulose, hydroxymethyl cellulose
Capsule filing process
Blending ingredients (excipents and active) Loading of capsules (body end downwards) Separation of caps and body (vacuum separation)
Automated filling process
Dosing of fill material (fill, replace the cap and eject)
Cleaning and polishing (remove powders adhere to shell)
Quality assurance
Uniformity of mass and content
- Check for homogeneity in weights and chemical analysis for uniformity
Disintegration (will it break apart in a reasonable time)
Dissolution testing
Dissolution testing
Measure the rate at which drug is released from the capsule
Capsule from manufacturer to pharmacist?
Raw material/capsule shelf Storage Quality control Weighing Mixing Packing Quality control Polishing FIlling Quality control Finished capsules Quality control Storage Delivery Pharmacist
Liquid filled hard gelatin capsules
Must not dissolve or alter the shell
Thixotropic formulation, thermal-Setting/thermosoftened
Mixed thermal-thixotropic system
Thixotropic formulation
Shear thinning –> pumpable
Agitation stops, system rapidly reestablishes a gel structure –> avoid leakage
Liquid excipents and gell forming agent
Thermal-setting/Thermosoftened formulation
Excipients used are liquid at filling temp but gel or solidifiy in the capsule
Contains PEG or poloxamer
Mixed-thermal-Thixotropic systems
Improved resistance to leakage
Sealing of liquid filled hard gelatin capsules
Sealed by coating the gap between the cap and body with a layer of gelatin called banding
Soft gelatin capsules
Single unit dosage forms that contain liquid or semisolid fill enveloped by a one pience hermitically sealed elastic outer layer
Composition of soft gelatin capsules
Gelatin
Plasticizers (glycern, sorbitol, propylene glycol)
Ratio of plasticizers to gelatin determine hardness
+ dyes, opacifiers, preservatives
Filling composition?
Lipophilic solutions, suspensions, low melting point drugs (vit A, D, E)
PEG
Self emulsifying systems
Micro-emulsions
Advantages of soft gelatin capsules
Higher degree of content uniformity Easier Enhanced bioavailability Hermitically sealed Wide variety
Disadvantages of soft gelatin capsules
More likely to interact with gelatin
Proteolytic activity disrupt the shell
Oily vehicles migrate to the shell
Rotary Die Process
Shell material is converted into the liquid state in jacketed tanks
Spreader boxes are fed with shell forming material from tank
Shell ribbons are formed by a rotating casting drum
Ribbons are then guided over counter rotating rolls containing sharp-edged dies
Each die cavity has the size and shape of half of the capsule to be formed
While passing through the rolls, the two ribbons form a sack like structure
Sacks are filled with drug materials
As the shell ribbon pass between the die rolls, the capsules will be fully sealed
Defects for filled hard gelatin capsules
Presence of cracks, pinholes Uniformity Capsule is empty Surface spot and contamination Free from particulate substances Undesirable odor Void space of the container should be filled
Minor defects filled hard gelatin capsules
Presence of pits and dents
Surface of the capsules are not smooth
Presence of particulate substance on the surface
Presence of spots or blemishes
