|
CAPSULES Objective: The student should be able to accurately calculate and prepare the capsule dosage form. The student should also be competent in knowledge of legal aspects of compounding controlled substances. Much of the background necessary to prepare the prescriptions for this lab was covered in PHRM4200 (Pharmaceutics I) and in PHRM3200 (Pharmacy Calculations). The International Journal of Pharmacy Compounding is a useful resource for information regarding specific formulations for capsules. With this background information, and with the practice of "packing" capsules by hand, you will become comfortable with the preparation of this dosage form. The USP defines a capsule as a "solid dosage form in which the drug is enclosed in either a hard or a soft, soluble container or 'shell' of a suitable form of gelatin". While tablet dosage form comprises a larger share of the drug market, patients surveyed seem to prefer the capsule dosage form. There are many advantages to the capsule which could account for this preference. A capsule is relatively easy to swallow and identify by the patient. It is pharmaceutically elegant and can conceal objectionable odor or taste. Capsules may be preferred by the pharmacist based on their ease of formulation, limited potential for incompatibilities, adaptability for individual dosing, and flexibility in onset and duration of action. There are some compounding problems which may be disadvantageous for the capsule. Very soluble substances such as potassium or calcium chloride, potassium bromide, or ammonium chloride pose a problem with the capsules as a form of administration because when the partly dissolved capsules comes in contact with the stomach wall, the concentrated solution of the substance can cause local irritation and gastric distress. The gelatin shell of a capsule will usually dissolve within 10 to 20 minutes after ingestion, although this can vary based on the ingredients inside the capsule. SOFT CAPSULES Soft gelatin capsules are one pieced and hermetically sealed. They are available in many sizes and shapes, and may be intended for oral, rectal, topical, or vaginal use. Soft gelatin capsules are made from gelatin, plasticizers, water, preservatives, coloring agents, and opaquants. Active ingredients administered in the form of soft gelatin capsules are first dissolved or dispersed in a suitable vehicle such as an oil or polyethylene glycol. Soft gelatin capsules are made from continuous gelatin ribbons which are brought together by two rotating dyes. The fill material is injected to swell the ribbons into half capsules, then the capsules are sealed together. The glycerin/water content of the soft
gelatin capsule may produce incompatibilities with some medicating agents.
Compounds such as aspirin hydrolyze readily, and would not be suitable for
administration in the soft gelatin capsules. Liquids with a pH below 2.5 or
above 7.5 would be incompatible with the shell material. Extemporaneous
compounding of soft gelatin capsules by the pharmacist is not possible.
HARD CAPSULES Hard gelatin capsules are made from a mixture of gelatin, sugar, and water, with the addition of plasticizers, coloring agents, and opaquants to give each capsule a distinguishable appearance. The amount of water or degree of hydration in a hard gelatin capsule should be maintained to avoid the capsule softening or becoming brittle. All hard gelatin capsules consist of two parts: a long, narrow section called the "body" and a shorter, wider portion called the "cap". These two portions telescope together and enclose the medicaments and excipients, and this procedure can be easily performed by the pharmacist. Empty hard gelatin capsules are available from various manufacturers ranging in size from 000 (the largest) to 5 (the smallest). Since the density and compressibility of a powder will vary, there are no strict rules in determining capsule size. The pharmacist may select the actual size needed for capsule preparation by packing capsules of various sizes with the mixture (or primary component thereof) to be packed in the capsules. The capsules are then weighed, and the most appropriate size determined. The micromeritics laboratory exercise in this course gave the student experience with this step. A guideline of capsule capacity is given below.
*
Actual weight is dependent on the density of the specific powder(s)
The weight of the contents of each capsule
is called the "target weight", and is calculated by adding the
weight(s) of all active ingredient(s) and the weight(s) of all excipient(s).
The
target weight may also specified by the physician or
decided upon by the pharmacist. If a tablet triturate is used, remember to include the total triturate weight, not just the weight of the active ingredient in that crushed tablet mixture. A target weight may be chosen arbitrarily, within the limits of the capsule size, and diluent weight calculated based on what target weight has been chosen. Powder mixtures intended for capsule administration are prepared in the same manner as powders administered as charts. The powder mixture is prepared (usually in a mortar and pestle to ensure thorough mixing and particle size reduction) and placed on a parchment pad. The powder is then compacted with a spatula blade to a depth of about one-third the length of the capsule. Then the body of the capsule is pressed into the powder firmly. This procedure is repeated until the capsule is filled. The cap is then placed on the body of the capsule. The capsule is then weighed on a balance, on which an empty gelatin capsule (of the same size as the one which is being filled) is placed. If the capsule is too heavy, the cap is removed and the capsule rotated gently between the thumb and forefinger to expel a small amount of powder, then the cap replaced and the weighing procedure repeated. If the capsule is too light, the cap may be easily removed and the body of the capsule "punched" into the powder mixture again to fill more completely. When all capsules have been filled to the
appropriate weight, the capsules are then cleaned to remove any smudges,
fingerprints, or excess powder. By rubbing the capsules with a towel
moistened with alcohol or by swirling the capsules in a beaker or flask with
sucrose crystals, all but the most stubborn problems will be removed.
Surgical gloves or finger cots may be worn during the packing procedure to
prevent fingerprints, or hands can be dusted with powder to prevent sweaty
hands. SPECIAL SITUATIONS Capsules lend themselves to ease of extemporaneous compounding, but there are some special situations which are worth mentioning. Liquids. Oils and other liquids in which the gelatin capsules are insoluble may be delivered by the capsule. The measured liquid is delivered into the body of an appropriate size capsule by a dropper. A cotton-tipped applicator is moistened (with water) and rubbed gently along the inside of the cap. The cap is then placed on the body with a firm twist to seal the capsule. Hygroscopic substances. Substances which absorb water from the atmosphere are best mixed with an equal weight of an absorbent diluent such as starch if administered by a capsule. Compounds which exhibit hygroscopic characteristics include the bromide, chloride, and iodide salts of the ammonium ion, calcium bromide and calcium chloride, ephedrine sulfate, hyoscyamine hydrobromide and sulfate, iron and ammonium citrate, lithium bromide, pepsin, phenobarbital sodium, salts of physostigmine, pilocarpine alkaloid, potassium acetate and citrate salts, sodium bromide, sodium iodide, sodium nitrate, and zinc chloride. Eutectics. Drugs or mixtures of drugs which liquefy to be administered concurrently within the same capsule are usually mixed with an absorbent diluent such as starch, kaolin, or light magnesium oxide. This serves both to physically separate the substances and to absorb any liquid which has accumulated. Usually it is necessary to add 120 mg of diluent for each capsule. Another method by which to separate two interacting compounds is to place one of the substances in a small capsule which is then placed in the larger capsule along with the other ingredients. Crystalline substances. Some drug substances to be packed in capsules do not form a compact powder mixture in which to punch the capsules. Aspirin and other crystalline drug are examples. Using easily compressible diluents such as starch seems to alleviate this problem. Another method to approach this problem is to scoop the body of the capsule through the powder mixture, then press the blade of a spatula against the opening to prevent the mixture from spilling.
Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems, 8th Ed., Chapter 7. Remington: The Science and Practice of Pharmacy, 19th edition A Practical Guide to Contemporary Pharmacy Practice, Judith E. Thompson, 2nd Ed., Chapter 25. |
