In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms—techniques used to enclose medicines—in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are:
Hard-shelled capsules, which contain dry, powdered ingredients or miniature pellets made by e.g. processes of extrusion or spheronization. These are made in two halves: a smaller-diameter “body” that is filled and then sealed using a larger-diameter “cap”.
Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil.
Both of these classes of capsules are made from aqueous solutions of gelling agents, such as animalprotein or plant polysaccharides or their derivatives. Other ingredients can be added to the gelling agent solution including plasticizers such as glycerin or sorbitol to decrease the capsule's hardness, coloring agents, preservatives, disintegrants, lubricants and surface treatment. Since their inception, capsules have been viewed by consumers as the most efficient method of taking medication. For this reason, producers of drugs such as OTC analgesics wanting to emphasize the strength of their product developed the “caplet”, a portmanteau of “capsule-shaped tablet”, in order to tie this positive association to more efficiently-produced tablet pills, as well as being an easier-to-swallow shape than the usual disk-shaped tablet.
Single-piece gel encapsulation ("soft capsules")
In 1833, Mothes and Dublanc were granted a patent for a method to produce a single-piece gelatin capsule that was sealed with a drop of gelatin solution. They used individual iron molds for their process, filling the capsules individually with a medicine dropper. Later on, methods were developed that used sets of plates with pockets to form the capsules. Although some companies still use this method, the equipment is no longer produced commercially. All modern soft-gel encapsulation uses variations of a process developed by R. P. Scherer in 1933. His innovation used a rotary die to produce the capsules. They were then filled by blow molding. This method was high-yield, consistent, and reduced waste. Softgels can be an effective delivery system for oral drugs, especially poorly soluble drugs. This is because the fill can contain liquid ingredients that help increase solubility or permeability of the drug across the membranes in the body. Liquid ingredients are difficult to include in any other solid dosage form such as a tablet. Softgels are also highly suited to potent drugs, where the highly reproducible filling process helps ensure each softgel has the same drug content, and because the operators are not exposed to any drug dust during the manufacturing process. In 1949, the Lederle Laboratories division of the American Cyanamid Company developed the "Accogel" process, allowing powders to be accurately filled into soft gelatin capsules.
Two-piece gel encapsulation ("hard capsules")
James Murdoch of London patented the two-piece telescoping gelatin capsule in 1847. The capsules are made in two parts by dipping metal pins in the gelling agent solution. The capsules are supplied as closed units to the pharmaceutical manufacturer. Before use, the two halves are separated, the capsule is filled with powder or more normally pellets made by the process of Extrusion & Spheronization and the other half of the capsule is pressed on. With the compressed slug method, weight varies less between capsules. However, the machinery required to manufacture them is more complex. The powder or spheroids inside the capsule contains the active ingredient and any excipients, such as binders, disintegrants, fillers, glidant, and preservatives.
Manufacturing materials
Gelatin capsules, informally called gel caps or gelcaps, are composed of gelatin manufactured from the collagen of animal skin or bone. Vegetable capsules are made up of cellulose, an important structural component in plants. To be more specific, the main ingredient of vegetarian capsule is hydroxypropyl methyl cellulose. In the current market, gelatin capsule is more broadly used than vegetarian capsule because its cost of production is lower.
Manufacturing equipment
The process of encapsulation of hard gelatin capsules can be done on manual, semi-automatic and automatic capsule filling machines. Softgels are filled at the same time as they are produced and sealed on the rotary die of a fully automatic machine. Capsule fill weight is a critical attribute in encapsulation and various real time fill weight monitoring techniques such as near-infrared spectroscopy and vibrational spectroscopy are used, as well as in-line weight checks, to ensure product quality. Volume is measured to the fill line, which is customarily to the top of the smaller-diameter body half. After capping, some ullage volume remains in the finished capsule.
Standard sizes of two-piece capsules
Drug-Embedded Empty Capsule Shells
A new class of capsules have been developed where drugs can be embedded in the capsule shell matrix.This allows different drugs to be delivered using the same capsule.The drug might be in a solubilized form, suspended form or chemically bound form in the capsule shell matrix. The drug can be in the cap of the capsule, body of the capsule or in both body and cap of the capsule. One can embed more than one drug in the capsule shell matrix. The drug can be in the dissolved and suspended form in the capsule shell matrix. Thus, one can create various types of variations in these "drug-embedded capsules". The rate of release of drug can vary based on the way drug is embedded in the capsule shell matrix and drug properties.