Soft & Hard Gelatin Capsule | Formulation Development

Overview of the formulation development of soft capsules, hard capsules & HPMC capsules & more on leading CDMOs, CROs offering capsule development.

Q1. What are pharmaceutical capsules?

In pharmacy, capsules refers to solid dosage forms in which drug substances or APIs and inert ingredients are enclosed in a hard or soft soluble container, usually of a form of gelatin. The shell is normally made from gelatin or other suitable polymeric material and results in a simple, tasteless, odourless, elegant, easy-to-swallow dosage form without the need for a secondary coating step.

Capsules are easy to manufacture and don't have any complex formulation requirements. Due to its ease of manufacturing and packaging, capsules are one of the most commonly used pharmaceutical dosage forms. Capsules are intended to be swallowed whole by the patient. In instances where patients (especially children) are unable to swallow capsules, the contents of the capsule can be removed and added to food prior to ingestion.

Capsules are available in various shapes and sizes and contain a single dose of one or more active pharmaceutical ingredients (APIs). They are a safe alternative to tablets and offer numerous benefits over the tablet form. Capsules are traditionally made from gelatin, an animal protein derived from collagen. In recent years, however, plant-based alternatives such as HPMC and modified starch have come into the market to cater to vegetarians.

Capsules may be filled with a range of formulation types including dry powders, semisolids, non aqueous liquids, and other dosage forms such as beads, mini tablets, and even mini capsules most of which are intended for oral administration as oral solid forms.

There are various contract development and manufacturing organizations (CDMOs) that offer CDMO services and drug delivery technologies for the formulation development and contract manufacturing and packaging of solid oral forms such as capsule drug products.

Some Advantages of Capsule Dosage Forms:

- Tasteless and odorless formulations.

- Easy to handle and carry.

- Unique mixes of ingredients are possible.

- Capsules can be opened to obtain powdered ingredients.

- Capsules are effective oxygen barriers and have excellent chemical stability.

Q2. What are the different types of capsules?

Capsules are dosage forms that encapsulate an active pharmaceutical ingredient (API) in a dissolvable shell. To meet the dynamic demands of the pharmaceutical industry, various types of capsules are used which include soft gelatin capsules, hard gelatin capsules, HPMC capsules, etc. These are explored in detail below.

Depending on the ingredients used in the capsule shell, capsules can be divided into non-veg gelatin capsules or vegetarian HPMC capsules.

- HPMC Capsules

For people with dietary restrictions, alternate dosage forms such as vegetarian HPMC capsules are available. HPMC capsules use hydroxypropyl methylcellulose as the main ingredient for the capsule body and cap. It is a safe drug for human consumption and a good alternative for gelatin capsules because of the vegetable source.

- Gelatin Capsules

Gelatin is an animal protein used to make capsules, which can deliver measured amounts of products. The pharmaceutical quality gelatin used in two-piece hard-shell capsules is obtained through the processing of collagen, a protein composed of eighteen different amino acids found in the connective tissues and bones of most animals, including humans.

Depending on the makeup of the gelatin capsule it can be divided into two types, hard capsules or two-piece capsules and soft capsules or one-piece capsules. The raw materials used in both types of capsules are similar. Both contain gelatin, water, colorants, preservatives, etc. In addition, soft capsules contain various plasticizers and glycerine.

- Soft Capsules

A soft capsule is a film formed into a certain shape while filling it with a liquid or paste. It can be used in many ways including a simple container (not to be ingested), to be swallowed whole, or to be used by crushing it. Compared with hard capsules, soft gelatin capsules are thicker and require additional ingredients such as glycerin to obtain their soft texture.

Perfectly suited for liquid capsule filling or semi-solid fillings, soft capsules are widely used to deliver pharmaceutical substances and a wide range of nutraceutical supplements, such as omega-3 fish oils. Many consumers prefer soft gelatin capsules over hard capsules as they are easy to use and swallow.

- Hard capsules

Hard capsules are normally employed for dry solid active pharmaceutical ingredients (APIs). The capsules are manufactured in two halves – a body and cap – to assist with filling. Gelatin has been the material of choice for hard capsules because of the ability of a solution to gel and form a solid oral form just above room temperature.

Traditionally hard capsules are made from gelatin and now also from hypromellose, which serve as a vegetarian alternative. Depending on the inner fill, hard capsules can be further divided into liquid filled hard capsules created via liquid capsule filling technology and dry filled hard capsules.

- Dry Filled Hard Capsules

Capsules that are filled with dry ingredients such as powders, granules, beads, tablets, pellets, etc. are referred to as dry filled hard capsules (DFCs).

- Liquid Filled Hard Capsules

As seen above, hard gelatin capsules are usually filled with powders, granules, or tiny pellets. However, hard capsules with liquid fillings are referred to as Liquid Filled Hard Capsules (LHFCs).

Q3. What are the steps involved in the development and filling of capsules?

Prior to manufacturing capsules, during the development phase, formulation development teams offer design and optimization of capsule formulations. The formulation development of capsule dosage forms includes pre-formulation studies, excipient screening, chemical compatibility and relevance studies, filling of capsules, etc. Some of these pharmaceutical development services for oral solids are explored in detail below.

Before developing capsule formulations the suitability of active pharmaceutical ingredients (APIs) and added ingredients are characterized via preformulation studies on the basis of their physical, chemical, biochemical, and mechanical properties. This is done to develop stable, safe and effective dosage forms.

Excipients are widely used to formulate solid drug forms such as capsules. However, the capsule forming properties of these excipients are affected by the presence of additives and active ingredients. The formulation development of capsules may therefore entail excipient screening.

Screening methods are used to determine the excipients which will optimize the capsule formulations. Selected diluents (fillers), disintegrants, glidants, lubricants, wetting agents, etc. are then weighed to get the required quantities for development and manufacturing.

Formulation for soft gelatin capsules involves liquid capsule filling, rather than powder technology. Materials are generally formulated to produce the smallest possible capsule consistent with maximum stability, therapeutic effectiveness and manufacturing efficiency. Incase of hard gelatin capsules the inner fill material could either be dry (powder filled) or liquid.

After development is completed, empty gelatin capsule manufacturing proceeds in the following steps in order from first to last; Dipping, spinning, drying, stripping, trimming, joining, and polishing. Hard gelatin capsules further undergo powder or liquid capsule filling via hand operated methods, semi automatic capsule devices, or automatic filling machines.

Every machine has its own working method. The capsule filling machine works in a step-by-step process which starts with positioning the capsules in a capsule filling tray, the caps are then removed from the bodies of the capsules and filled with the inner fill materials. The caps and bodies are then rearranged and sealed after which the capsules are expelled from the machine.

In capsule formulation development and during the filling of capsules, a number of quality control tests are performed to ensure that the capsules produced meet the conventional requirements established by the pharmaceutical industry over the years.

A contract research organization (CRO) or a contract development and manufacturing organization (CDMO) which has clinical development and pharmaceutical development capabilities as well as contract manufacturing capabilities for solid-dosage forms can offer CDMO services for capsule drug products.

Q4. Which are the leading pharmaceutical companies offering the development of capsules?

Leading contract research organizations (CROs) and contract development and manufacturing organizations (CDMOs) having drug delivery technologies for the formulation development of capsule drug products for clinical and commercial manufacturing are noted below.

Quotient Sciences - Capsule Drug Product Development Services

Quotient functions as a contract research organization (CRO) and contract development and manufacturing organization (CDMO). Quotient has solid dosage capabilities and offers clinical development and CDMO services such as formulation development for solid oral forms including immediate, sustained and modified release tablets, multiparticulates, mini-tablets, granules, and orally disintegrating tablets (ODT) along with other oral formulations.

Pfizer CentreOne - Capsule Drug Product Development Services

Pfizer CentreOne has solid dosage capabilities and excels in the development and contract manufacturing and packaging of oral solid dosage forms such as capsules, tablets, granules and highly potent products for both clinical and commercial manufacturing.

Pfizer can optimize processes and scale up oral solid forms from clinical development to commercial manufacturing. It has integrated cGMP pilot facilities dedicated to process optimization, clinical drug manufacturing, and pharmaceutical development services for oral solids.

Recipharm AB - Capsule Drug Product Development Services

Recipharm offers formulation development or drug product development services for all common dosage forms including solid-dosage forms, tablets, mini tablets, capsules, hard gelatin capsules, injectables, semi-solids and liquids, etc.

It offers pharmaceutical formulation development contract services for all oral formulations. Recipharm has the resources to meet your project requirements whether you are looking for a small number of capsules to conduct a first-in-human study or if you need pharmaceutical development services for oral solids along with full-scale production.

Athena Pharmaceutiques - Capsule Drug Product Development Services

Athena S.A.S offers formulation development and manufacturing for various oral formulations such as capsules in bulk and finished packs, tablets in bulk and finished packs, pellets for filling in capsules, pellets or granules in sachets, etc.

It offers various pharmaceutical formulation development contract services for both finished and semi-finished products like pellets to be filled in capsules and granules ready for compression.

Eurofins CDMO - Capsule Drug Product Development Services

Eurofins CDMO has solid-dosage capabilities and offers solid-dosage forms (capsules, tablets), parenteral formulations, ophthalmics, topicals, etc. It provides formulation development services for a wide range of different drug delivery routes and drug delivery systems for clinical and commercial manufacturing.

Eurofins CDMO offers a full suite of pharmaceutical formulation development contract services encompassing preclinical development, formulation screening and pharmaceutical development capabilities, analytical development of oral solid forms for oral delivery, etc.