Compounding pharmacists are constantly faced with the challenge of finding ways to assist patients with their special drug requirements while ensuring the medications’ safe and effective use. And while there are many different ways to administer medications to patients, oral capsules have established an incredibly important role in drug delivery.

Capsules are a form of medication that encloses the carefully dosed active ingredient(s) in the form of powder, semisolid, or liquid drugs in an edible container (the capsule), and the medication is not released until the container or the capsule is disintegrated in the stomach. Some advantages can be realized by using capsules, namely, they can be prepared extemporaneously, they provide dosing flexibility, and capsules are available in different colors (solid colors, clear/translucent, and mixed colors) for convenient and easier identification. Using capsules as a mode of administration can also mask the bitter taste of some APIs. 

Capsules are commonly made of gelatin or cellulose. The first type would be the soft gelatin capsules that are one-piece, especially hermetically sealed shells. These capsules are commonly used to deliver liquid oral medications and are preferred for ingredients with poor water solubility and low melting points, and for medications that require ultra-low doses. 

The second type of capsule is the more common hard-shell variety that comes in 2 halves. This is by far the easiest to extemporaneously use, most easily available, and most versatile among all dosage forms. However, because gelatin capsules are made of hydrolyzed collagen from animals, the issue of vegetarian and nonvegetarian capsules is coming up with the understanding that food habits and preferences vary Therefore hard-shell capsules are further categorized into two types: gelatin, and Vegi-caps which are made to address this problem. Vegi-caps are composed of hydroxypropyl methylcellulose (HPMC, or Hypromellose) which is derived from vegetable cellulose. It is an all-natural ingredient that does not contain any animal by-products and can make all the difference for vegetarians and vegans. These types of capsules are available in our catalogue.

Compounding capsules

1. Prepare the API and excipients

Measure the ingredients, which can be in powder, tablets, capsules, and in liquid form. The powdered form ingredients are the most straightforward to make. For tablets, they have to be finely comminuted with a mortar and pestle, or special equipment to be incorporated in the capsule as a powder mix. Liquids, on the other hand, can 1. be evaporated to dryness and be used as a powder, 2. or can be soaked up by an adsorbent and then be combined into the powder mix, or 3. be filled in gelatin capsules as a liquid or as a semisolid mass. 

Prepare a sufficient quantity of the APIs and excipients. Measure or weigh the ingredients with your weighing scale and, if permitted, it would be ideal to produce an additional 5 to 10% of the formulation to allow for a margin of error for ingredient loss (this method does not apply for controlled substances). This is not a necessary step to take, however, if the compounder should like to maintain higher operational standards and have a more effective formulation, this is a great way to solve the common issue of powder or ingredient loss.

2. Homogenize the mixture 

Mix the ingredients by using a mortar, your spatula and surface, or by using  special equipment such as Gako’s new innovation: the InvoMatic which will compound ingredients into homogeneous mixtures at controlled time and speed, in any vessel, any volume, and without the need for cleaning afterward.

3. Select appropriate capsule size (and/or color)

There are 7 different sizes of gelatin capsules available at Xenex Labs with #4 being the smallest and #000 the largest. The numerical designations do not necessarily indicate a capsule’s capacity as it depends on the density and characteristics of the medication it will contain. See our capsule size chart for your reference. 

4. Encapsulate

Encapsulating the prescription can be done in 2 ways, first would be to hand fill the capsules. 

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This method requires the pharmacist to not touch the powder while punching the capsules and wearing gloves or finger cots will minimize contact and prevent leaving fingerprints on the capsules. Once capsules are hand-filled with their preferred tile or tool, the capsule would have to be weighed by a pharmaceutical or electronic laboratory balance and adjusted accordingly to achieve the dose desired. Capsules can also be filled by machine, which could potentially make up to 300 capsules at a time which can definitely improve pharmacy efficiency. 

5. Clean the capsules, then package

Cleaning capsules would be very difficult if the capsule capture moist or sticky, and it can cause capsules to stick together, creating an unsightly appearance and potentially an unpleasant taste as well, therefore the pharmacist must take every precaution to prevent this from happening, otherwise, the capsules would become soiled and cannot be effectively cleaned. If the capsules have been kept dry, excess powder on the capsules can be removed by shaking the batch in a cloth bag or mixing the filled capsules in a vessel with some salt (NaCl) crystals.  Vigorously mix the capsules in the salt then remove the salt via a fine mesh sieve. Package, label, and store the capsules as appropriate, while conforming to USP stability regulations.

Compounding prescriptions has played an important role in the pharmacy industry to help patients get their needed medications and in custom doses that are not commercially available, and pharmacists are responsible for ensuring the safety, efficacy, and quality of the compounded medications. And so with this in mind, compounding capsules has proven to be of importance because of ease of production and quality control, they can be made extemporaneously, and the flexibility of making capsules from the size, to color, to composition make them a great option for administering drugs.

References:

1. Gullapalli, R. P. (2010, October 1). Soft Gelatin Capsules (Softgels). Xenex Labs. Retrieved March 7, 2022, from https://www.jpharmsci.org/article/S0022-3549(15)32458-8/references
2. Prakash, A., Soni, H., & Sarma, P. (2017, September). Are your capsules vegetarian or nonvegetarian: An ethical and scientific justification. Xenex Labs. Retrieved March 7, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830853/?report=reader
3. Allen Jr, L. V. (2016). BASICS OF COMPOUNDING: Capsules. International Journal of Pharmaceutical Compounding, 20(2), 125-134.
4. Allen, L. V. (1998). The art, science, and technology of pharmaceutical compounding (Vol. 2). Washington, DC: American Pharmaceutical Association.

Reviewed by: Paul Gibbons B.Sc. Pharm. RPh.
March 15th, 2022