Mechanism of drug release of different types of oral dosage forms in pharmaceuticals.

Oral solid dosage has been a predominant form to provide Active Pharmaceutical Ingredients (APIs) to a patient. The disintegration of the drug through oral dosage forms has been a cause of major bioavailability problems in the past. Therefore, the mechanism is carefully controlled in pharmaceutical products. Oral dosage usually refers to the category of drugs administered to the patient in the form of tablets, capsules and other orally administered forms.

A tablet is one of the major forms of oral solid dosage of drugs. It consists of powder compacts that include different excipients and APIs. Excipients are added to tablets in order to obtain desired fill weight of a dosage form, to improve processability or to improve the drug release behavior. The drugs, when coming in contact with the physiological fluids, undergo several mechanisms.

Mechanism of Drug Release from Oral Dosage Forms

This is a specifically critical process for Immediate-release dosage forms. Immediate-release tablets are such that they completely disintegrate and dissolve within a short time period of 2.5 to 10 minutes when exposed to physiological fluids. Such fast disintegration is even more required for Orally-dispersible tablets that disintegrate in the mouth immediately after coming in contact with the saliva before being swallowed. Also, the quick disintegration of the drug is required in case of the need for rapid onset of action, For example – Analgesics.

Another form of tablets is the Modified-release tablets. In such dosages, API release may be designed to be slow for gradual or selective absorption in the Gastro-Intestinal (GI) tract, or for resulting in delayed onset time. This gradual disintegration can be obtained by- embedding API in a polymer matrix having slower dissolving rate than the drug, or by coating the API with a suitable polymer coating that functions as a mass transfer limiting barrier.

Estimation of an in-vivo performance of a pharmaceutical product on its in-vitro drug release profile by estimating empirical in-vivo in-vitro product development is a very frequently used practice these days. However, it has several drawbacks that result in incomplete process and understanding.

Usually, therapeutic dose of a drug is administered to the patient. In that case, API is combined with the excipients to obtain the required full volume of the dosage, hence, facilitating the compression of the powder mixture into desired tablet size. APIs can lead to several processing limitations such as – difficulty in blending, unwanted adhesion to surfaces of tablet punches and feeder walls, or poor flowability. These processing limitations of APIs occur due to their small particle size and needle-like morphology.

To overcome these limitations, selecting proper process routes like glidants, lubricants and surfactants are crucial in order to ensure a high-quality product. However, embedding of a drug in a complex matrix usually reduces its bioavailability. It delays the onset of dissolution in case of Immediate-release tablets.

Therefore, it is required to add disintegration agents to enhance breaking up of tablets in small granules and constituent particles and thus, facilitate quick disintegration of drug particles from the matrix of the tablet so as to increase the surface area for dissolution.

Synthetic polymers such as Crospovidone (XPVP), Croscarmellose Sodium (CCS) and Sodium Starch Glycolate (SSG) are the most commonly used disintegrants. The disintegration has a huge impact on the therapeutic effect of the medication and therefore, it needs to be evaluated and ideally quantified using specially designed disintegration tests.

The API near the tablet surface will dissolve, leaving the API in the matrix in the absence of disintegration. Hence, complete disintegration of the tablet upon exposure to the dissolution medium is very crucial to obtain a dependable clinical performance of the dosage form.