Untitled

• Capsules are solid dosage forms in which the drug substance is enclosed in either a hard or soft, soluble container or shell of gelatin.
• Capsules are easier to swallow than tablets.
• Capsules are often used in extemporaneous preparations.
• Capsules are the dosage form of choice in clinical trials.
• Capsule can be made of Gelatin, Methyl cellulose (HPMC), or Calcium alginate.
• Drcaps are gastro resistant capsules.

Gelatin manufacturing Process

• Gelatin is derived from skin or bone.
• Gelatin manufacturing requires acid or alkali treatment.
• Gelatin manufacturing involves extended treatment periods.
• The gelatin manufacturing process includes filtration and vacuum concentration.
• The gelatin manufacturing process requires cooling to solidify, air drying and milling to size.

Gelatin Manufacturing Process Types

• Type B gelatin is from the alkaline process, using split bovine hide and bone.
• Split is leather created from the fibrous part of the hide left once the top-grain of the rawhide has been separated from the hide.
• Type A gelatin uses an acid process, and pig skins
• Animal skin treated for human use is hide and can include leather from cattle and other livestock animals.

Manufacture of Hard Gelatin Capsules

• Mechanical dipping of metal (bronze) pins and pegs of desired shape and diameter are dipped into a gelatin solution with specific temperature and viscosity.
• Initial shells are dried with filtered air and trimmed.
• Bodies and caps are fitted together.
• Colorants like titanium oxide are added to gelatin causing opacity.

Quality Control and Stability of Empty Capsules

• Capsule bodies are subject to visual inspection to verify integrity, color, and shape.
• Capsule bodies also go through microbiological testing.

Formulation & Selection of capsule size

• Preformulation is necessary for capsule creation.
• You must select the quantity of powder and blend it.
• There are key ingredients like a bulking agent (lactose), a diluent/absorbent (kaolin), a glidant to improve flow (silicon dioxide), a lubricant (magnesium stearate), and a surfactant (sodium dodecyl sulfate).
• Capsule size selection is determined by powder properties like density, flow-ability, and compressibility.
• Filling and sealing are the final steps.

Capsule Size

• Various sizes are manufactured.
• Selection is based on the required quantity of formulation .
• Selection is strongly influenced by bulk density and compressibility.
• Pharmacists can compound capsules to address individual dosing needs, which offers advantages over tablets.

Capsule Size Example

• Capsule sizes range from 000 to 5, with volumes that range volumetrically from 1.37cm^3 to 0.21cm^3

Dosage Form Formulation

• Industrial scale involves thousands of capsules.
• Formulation is prepared to fill the number of capsules in the process, which involves tens if not hundreds of kilograms of material.
• Extemporaneous preparation involves 6-12 capsules.
• Enough is prepared to fill one capsule more than the required number to account for fill loss.
• For a controlled substance, the amount of drug utilized must correspond exactly with the prescription.

Hard Gelatin Capsule Filling Process

• Hard gelatin capsules undergo processes such as supply, rectification, separation, filling, joining, and discharge.

Flexible Use of Hard Gelatin Capsules

• Hard gelatin capsules can contain pellet mixtures, powder, granulate, solid formed drug preparations, 1st pellet type, 2nd pellet type, capsules, or paste.

Mechanics of Capsule Filling

• The method used can be reservoir (plate or single capsule filling) or auger feed.
• Capsule filling is done by tamping tool or utilizing positive displacement (continuous compression).

Capsule Closure

• Capsules can be spot welded with a heated metal pin, or bonded with molten gelatin.
• Capsules can utilize snap fit or Coni-snap closure mechanisms.

Storage and Stability

• Capsules are susceptible to microbial and structural effects from moisture leading to microbial growth, distortion and/or brittleness.
• Hygroscopic contents may require packaging with a desiccant.
• Gelatin dissolves in warm gastric fluid; it's digested and contents are released rapidly.

Examples of Hard Gelatin Capsules

• Amoxicillin (Viomox)
• Ampicillin (Omnipen)
• Cephalexin (Keflex)
• Fluoxetine HCl (Prozac)
• Indomethacin (Indocin)
• Levodopa (Larodopa)
• Oxazepam (Serax)

Soft Gelatin Capsules

• Shells of soft gelatin include glycerin or sorbitol added to the gelatin to induce plasticity.
• Soft gelatin capsules are oblong, elliptical, or spherical.
• Soft gelatin capsules can encapsulate liquids, suspensions, pastes, or dry powders.
• Soft gelatin capsules must be prepared, filled, and sealed in one continuous operation.

Soft Capsule Manufacture

• One of the manufacturing processes is the plate process utilizing molds and sheets of gelatin.
• Another manufacturing process is the die process, which involves either rotary or reciprocating methods.

Soft Gelatin Capsule Liquids

• Liquids appropriate for inclusion are water immiscible, volatile and nonvolatile liquids.
• Oily, non-volatile liquids are appropriate for inclusion .
• Low molecular weight compounds that can easily pass through the capsule are not appropriate for inclusion.

Examples of Soft Gelatin Capsules

• Amprenavir (Agenerase)
• Cyclosporine (Neoral)
• Digoxin (Lanoxicaps)
• Ethosuximide (Zarontin)
• Ranitidine HCl (Zantac GELdose)
• Ibuprofen (Advil)
• Nutraceuticals like Fish oil, Aloe vera, and Royal Jelly

Quality Control and Packaging for Final Dosage Form

• Part of final quality control is visual inspection for integrity, color, fill, and shape.
• Weight (uniformity, 85-115%), potency and uniformity in concentration of active, and microbiological testing are also part of final quality control.
• Packaging containers include glass, plastic and/or blister packs.