Capsules: Pharmaceutical Dosage Forms - PHAR 7624 Spring 2024 PDF

Capsules PHAR 7624 L. Garcia-Contreras, Ph.D. Pharmaceutics II Spring 2024  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsu...

Capsules PHAR 7624 L. Garcia-Contreras, Ph.D. Pharmaceutics II Spring 2024  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules  Capsules “Solid dosage forms in which the drug substance is enclosed in either hard or soft, soluble container or shell of a suitable form of gelatin” RE King and JB Schwartz, 1985 Easier to swallow than tablets Used in “Extemporaneous preparations” Dosage form of choice in Clinical Trials  Capsules Gelatin – Hard – Soft Methyl cellulose (HPMC) Calcium alginate DRcaps™ Gastro Resistant Capsules Courtesy of Capsugel Gelatin manufacturing Process Derived from skin or bone Acid or alkali treatment Extended treatment periods Filter Vacuum concentration Cool to solidify Air dry Mill to size  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules  Gelatin Manufacturing Process Hide: animal skin treated for human use. Include leather from cattle and other livestock animals 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 Gelatin world market Pig skins Bovine hides Bones Other Gelatin Processing Aids www.geafiltration.com  Gelatin Manufacturing Process Hide: animal skin treated for human use. Include leather from cattle and other livestock animals 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 Gelatin world market Pig skins Bovine hides Bones Other Gelatin Processing Aids www.geafiltration.com Manufacture of Hard Gelatin Capsules: MECHANICAL DIPPING Mechanical dipping Initial Shells Gelatin of metal (bronze) dried solution pins and pegs of (filtered air) desired shape and and trimmed *Temperature *Viscosity diameter Initial Shells bodies and caps fitted NB colorant used to color Final caps gelatin and titanium oxide and causes opacity bodies Mechanical Dipping http://www.youtube.com/watch?v=0EwaIQ-U6QQ  Quality Control and Stability of capsule bodies (empty capsules) Visual inspection – integrity, color, shape Microbiological testing  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules Formulation and Selection of Capsule Size Preformulation Selection of quantity of powder/Blending Ingredients – Bulking agent e.g. lactose – Diluent/Absorbent e.g. Kaolin – Glidant (improves flow) e.g. silicon dioxide – Lubricant e.g. magnesium stearate – Surfactant e.g. Sodium dodecyl sulfate Selection of capsule size (ρ, ε, flow-ability, CCI) Filling/Sealing  Capsule Size Various sizes are manufactured Selection based on quantity of formulation required Influenced by bulk density and compressibility No strict rules apply Pharmacist can compound to address individual dosing needs which offers advantage over tablet. Capsule size 17  Selection of Capsule Size: Example You are the pharmacist at an in-patient pharmacy of the local hospital and you are asked to prepare capsules with a specific medication for a patient, who needs 250 mg of a drug-excipient powder blend that has an apparent density of 0.85 g/cm3. What capsule number would you use so that the powder fits without being compacted and without having excess void space in the capsule? 𝑚𝑚 𝜌𝜌′ = 𝑉𝑉 0.25 𝑔𝑔 This is the volume 𝑚𝑚 = 0.2941 cm3 V= = 𝑔𝑔 occupied by 250 mg 𝜌𝜌′ 0.085 of the powder blend 𝑐𝑐𝑐𝑐3 A #3 capsule will be sufficient to encapsulate the powder blend for this patient 18  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules  Formulation of Dosage Form Industrial scale (Thousand of capsules) – Formulation is prepared to fill the number of capsules in the process (Tens if not hundreds of Kilograms of material) Extemporaneous Preparation (6-12 capsules) - Prepare enough to fill one capsule more than 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 https://www.youtube.com/watch?v=r2FYbmwV_iU Flexible Use of Hard Gelatin Capsules Paste http://www.youtube.com/watch?v=zZGgffKpJCI&feature=related  Mechanics of Capsule Filling Reservoir (plate or single capsule method) Auger Feed Tamping tool Positive displacement (Continuous compression  Capsule Filling Reservoir Auger  Capsule Closure Spot welded with heated metal pin Bonded with molten gelatin Snap fit Coni-snap Courtesy of Capsugel  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules  Storage and Stability Susceptible to microbial and structural effects of moisture – Microbial growth – Distortion (loss of rigidity)/Brittleness Hygroscopic contents may require packaging with desiccant Dissolves in warm gastric fluid. Gelatin is digested and contents released rapidly  Examples of hard gelatin capsules Amoxicillin (Viomox) Ampicillin (Omnipen) Cephalexin (Keflex) Fluoxetine HCl (Prozac) Indomethacin (Indocin) Levodopa (Larodopa) Oxazepam (Serax)  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules  Soft gelatin capsules Shells of soft gelatin – Glycerin or sorbitol added to the gelatin to induce plasticity (to “plasticize” (make the gelatin moldeable)) Oblong, elliptical or spherical shape Used to encapsulate liquids, suspensions, pastes or dry powders Must be prepared filled and sealed in one continuous operation  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules  Soft capsule manufacture Plate process – Molds used to form capsules. – Liquid medication poured on warm sheet of gelatin placed on bottom plate of mold. – Second sheet of gelatin placed above medication and top mold is put in place. – Entire mold is pressed to form fill and seal capsules simultaneously Die Process – Rotary – Reciprocating  Soft capsule manufacture Plate process – Molds used to form capsules. – Liquid medication poured on warm sheet of gelatin placed on bottom plate of mold. – Second sheet of gelatin placed above medication and top mold is put in place. – Entire mold is pressed to form fill and seal capsules simultaneously Die Process – Rotary – Reciprocating  Soft gelatin capsule manufacture https://www.youtube.com/watch?v=pu9bvGlCxVc Liquids for inclusion in soft gelatin capsules Water immiscible, volatile and nonvolatile liquids Oily, non-volatile liquids Not suitable for low molecular weight compounds that can easily pass through the capsule  Examples soft gelatin capsules Amprenavir (Agenerase) Cyclosporine (Neoral) Digoxin (Lanoxicaps) Ethosuximide (Zarontin) Ranitidine HCl (Zantac GELdose) Ibuprofen (Advil) Nutraceuticals – Fish oil – Aloe vera – Royal Jelly  LEARNING OBJECTIVES: Capsules 1. Name the 2 processes to obtain the gelatin used in capsule manufacture 2. Explain the procedure and rationale used in the powder formulation and selection of a capsule size 3. List the procedures employed to fill hard gelatin capsules 4. Describe the factors that affect the stability of a hard gelatin capsule 5. Name the ingredients to manufacture soft gelatin capsules and explain their function within the formulation 6. Describe the processes to manufacture soft gelatin capsules 7. List the determinations performed for the quality control of finished capsules  Final dosage form: Quality Control and Packaging Visual inspection – integrity, color, fill, shape Quality control – Weight (uniformity, 85-115%) – Potency and uniformity in concentration of active – Microbiological testing Packaging in glass/plastic/blisters.