Capsules: Topic 2 (PDF)

PCTS1-DDS Capsules Jefferson A. Chanco RPh Objectives After reading this chapter, the student will be able to: 1. Differentiate between hard gelatin and soft gelatin capsules 2. Compare and contrast advantages and disadvantages of hard gelatin and soft gelatin capsules 3. List categories of in...

PCTS1-DDS Capsules Jefferson A. Chanco RPh Objectives After reading this chapter, the student will be able to: 1. Differentiate between hard gelatin and soft gelatin capsules 2. Compare and contrast advantages and disadvantages of hard gelatin and soft gelatin capsules 3. List categories of inert ingredients, with examples, which are employed in the compounding or manufacture of capsules 4. State USP compendial requirements for capsules 5. Define and differentiate weight variation from content uniformity 6. Describe appropriate techniques for compounding, inspecting, packaging, and storing capsules Overview of Capsules Capsule Advantages Mask odor and/or taste of unpleasant drugs Easy to prepare Can vary dosage and combination of drugs Capsules Hard gelatin capsules Soft gelatin capsules Compendial requirements for capsules Official and commercially available capsules Inspecting, counting, packaging, and storing capsules Definitions/Types Unit doses of powder, semisolid or liquid drugs enclosed within either a hard or a soft envelope, or shell Hard gelatin capsules Soft gelatin capsules Historical Use 1833 Mothes, a French pharmacist Soft gelatin capsule 1833 Dublanc Improved the capsule 1834 Patents issued to both 1846 Patent to Lehuby, hard capsule 1848 Murdock, two-piece hard gelatin capsule, patented in 1865 1934 Robert Pauli Scherer invented a machine—a rotary die press—that could produce soft gelatin capsules to contain medications. Capsules with Special Names Kapseals Spansule capsules Ped caps Minimicrospheres Applications Place on tongue and swallow with liquid Dissolve contents in water or mix contents with food Rectal and vaginal Capsule Disadvantages Not suitable for administering very soluble ionic salts (e.g., potassium chloride, ammonium chloride) Hard Gelatin Capsules Hard Gelatin Capsules The manufacture of hard gelatin capsule shells Capsule Preparation Equipment Materials Supplies Capsule Preparation (cont.) 1. Comminution 2. Blending 3. Determine capsule size 4. Add additional diluent prn 5. Encapsulate 6. Clean 7. Quality control 8. Package and label Comminution Similar particle size Mortar and pestle Pill tile and spatula Mill Levigation Pulverization by intervention Other Blending Uniform distribution of actives in the matrix Mortar and pestle Pill tile and spatula Bottle Plastic bag Other Use of tracer/color Determine Capsule Size Human Veterinary Volume occupied Rule of 6’s- capsule sizes 0,1,2,3,4 and 5 can hold 6-7, 5, 4, 3, 2 and 1/2-1 grains of the powders, respectively. Rule of 7’s Capsule Sizes: Human 000 00 0 1 2 3 4 5 Capsule Sizes: Veterinary Designation Nominal powder weight 7 1.5 ounce 10 1 ounce 11 0.5 ounces 12 0.25 ounces 13 0.125 ounces Capsule Packing Statistics Capsule Size Powder 5 3 1 0 Aspirin 65 195 325 490 mg Calcium carbonate 120 280 460 600 mg Cornstarch 130 270 440 580 mg Lactose 140 280 460 600 mg Sodium bicarbonate 130 325 510 715 mg Volume Occupied Rx Drug A 25 mg (250 mg filled) Drug B 50 mg (200 mg filled) Lactose qs size #1 capsule (400 mg) 25/250 = 10% 50/200 = 25% 10% + 25% = 35% 100% − 35% = 65% 400 mg  65% = 260 mg lactose per capsule Rule of 6’s (Approximation) Set up 6 6’s 6 6 6 6 6 6 List cap size 0 1 2 3 4 5 Subtract (gm) 6 5 4 3 2 1 Convert (mg) 390 325 260 195 130 65 Rule of 7’s (Approximation) Convert weight of powder to grains. Subtract from “7” and match below: −3 000 −2 00 − 1 or 0 0 +1 1 +2 2 +3 3 +4 4 +5 5 Complete the Formula Rx – Drug quantities – Diluent quantities Colored Capsules Record size and color of capsule used Colored powders Encapsulate Individual hand filling Capsule machine filling Filling capsules with a semisolid mass Filling capsules with liquids Cleaning Capsules Minimize traces of dust, moisture, etc. Dedusting using a cloth or screen or salt bottle. Most cleaning procedures are effective only if the capsules have been kept clean and dry. Capsule Closure Lock-caps available Hot pin Moist towel Gelatin band Identification: “It appears to be…” NOT “It is…” Developing the Formulation and Selection of Capsule Size Accurate dosage Good bioavailability Ease of filling and production Stable Elegant Physicochemical Considerations Incompatibilities Hygroscopic Deliquescent Eutectic Use of diluents/adsorbents Special Applications and Considerations Potent powders Tablet with a capsule Capsule within a capsule Altered-release capsules Rapid-release capsules Special Problems Deliquescent powders Eutectic mixtures Potent powders Tablet with an capsule Capsule within a capsule Masses/semisolids Oils Filling Hard Capsule Shells Punch method Capsule machine (100 count, 300 count, etc.) Automated machines Capsule Sealing Kapseals Gelatin bands Heat welded or thermally coupled Cleaning and Polishing Capsules Cleaning vacuum Clean gauze or cloth Soft Gelatin Capsules Preparation of Soft Gelatin Capsules Plate process Molds Rotary die process Use of Soft Gelatin Capsules Water-immiscible volatile and nonvolatile liquids Water-miscible nonvolatile liquids Water-miscible and relatively nonvolatile compounds  Compendial Requirements for Capsules Capsule Quality Control Drug content Fill weight Disintegration Dissolution Stability Added Substances Harmless Do not exceed minimum amounts required Do not impair bioavailability Do not interfere with compendial assays and tests Containers for Dispensing Capsules Tight Well-closed Light-resistant Disintegration Test for Capsules Basket rack assembly 37°C water or suitable fluid Disintegrate completely into a soft mass with no palpable firm core and only some fragments of the gelatin shell Dissolution Test for Capsules Paddle method Basket method Weight Variation Hard capsules Soft capsules Content Uniformity 9 of 10 within 85% to 115% None outside of 70% to 125% of label claim Additional testing required if they are outside Content Labeling Requirement All official capsules must be labeled to express the quantity of each active ingredient in each dosage unit. Stability Testing Intrinsic stability of the active drug molecule Environmental factors: temperature, humidity, light, formulative components, and container and closure system Stability USP Pharmacy Compounding 6 months if prepared from USP/NF ingredients 25% of remaining expiration dating if prepared from commercial products Unless evidence is available to support other dating Moisture Permeation Test Single- and unit-dose containers  Inspecting, Counting, Packaging, and Storing Capsules Packaging/Storage Room temperature, generally Determined by active drug Oral Administration of Solid Dosage Forms Patient Counseling Capsules #0 through #5 are not difficult to swallow. Larger capsules: use syrup, honey, liquid candy to help the patient swallow. Caution when emptying contents to food, etc. Other routes of administration. Capsule Administration Place on tongue and swallow with liquid. Dissolve contents in water or mix contents with food. Morphine Sulfate 10-mg and Dextromethorphan HBr 30-mg Capsules Morphine sulfate 1g Dextromethorphan HBr 3g Lactose 35.5 g Fill 100 #1 capsules Progesterone 100 mg in Peanut Oil Capsules Micronized progesterone 10 g Peanut oil qs 30 mL Using a micropipette, add 300 μL into each capsule. Triple Estrogen Capsules, Semisolid Fill Estriol 200 mg Estrone 25 mg Estradiol 25 mg Polyethylene glycol 1450 20 g Polyethylene glycol 3350 20 g End of Discussion