Controlled Release Medication

Controlled Release Medication

An ideal dosage regimen in the drug therapy of any disease is the one which immediately attains the desired therapeutic concentration of drug in plasma (or at the site of action) and maintains it constant for the entire duration of treatment. This is possible through administration of a drug delivery system in a particular dose and at a particular frequency. The term drug delivery covers a broad range of techniques used to get therapeutic agents into the human body. The frequency of administration or the dosing interval of any drug depends upon its half-life or mean residence time (MRT) and its therapeutic index. When a drug is delivered as a conventional dosage form such as a tablet, the dosing interval is much shorter than the half-life of the drug resulting in a number of limitations associated with such a conventional dosage form:

1. Poor patient compliance; increased chances of missing the dose of a drug with short half-life for which frequent administration is necessary.

2. A typical peak-valley plasma concentration-time profile is obtained which makes attainment of steady-state condition difficult (see Fig. 14.1).

3. The unavoidable fluctuations in the drug concentration may lead to under-medication or over-medication as the C_ss values fall or rise beyond the therapeutic range.

4. The fluctuating drug levels may lead to precipitation of adverse effects especially of a drug with small therapeutic index whenever overmedication occurs.

There are two ways to overcome such a situation –

1. Development of new, better and safer drugs with long half-lives and large therapeutic indices, and

2. Effective and safer use of existing drugs through concepts and techniques of controlled and targeted delivery systems.

The first approach has many disadvantages which therefore resulted in increased interest in the second approach. The second approach, owing to several technical advancements, has resulted in the development of drug delivery systems capable of controlling the rate of drug delivery, sustaining the duration of therapeutic action and/or targeting the delivery of drug to a particular tissue. An ideal drug delivery system should deliver the drug at a rate dictated by the needs of the body over a specified period of treatment. This idealized objective points to the two aspects most important to drug delivery –

·           Spatial delivery of drug which relates to targeting a drug to a specific organ or tissue, and

·           Temporal delivery of drug which refers to controlling the rate or specific time of drug delivery to the target tissue.

An appropriately designed controlled-release drug-delivery system (CRDDS) can improve the therapeutic efficacy and safety of a drug by precise temporal and spatial placement in the body, thereby reducing both the size and number of doses required (see Figure 14.1).

Fig. 14.1 A hypothetical plasma concentration-time profile from conventional multiple dosing and an ideal controlled delivery formulation

The several advantages of a controlled drug delivery system over a conventional dosage form are—

1. Improved patient convenience and compliance due to less frequent drug administration.

2. Reduction in fluctuation in steady-state levels (Fig. 14.1) and therefore –

^·            Better control of disease condition, and

^·            Reduced intensity of local or systemic side-effects.

3. Increased safety margin of high potency drugs due to better control of plasma levels.

4. Maximum utilization of drug enabling reduction in total amount of dose administered.

5. Reduction in health care costs through –

^·            Improved therapy

^·            Shorter treatment period

^·            Lower frequency of dosing, and

^·            Reduction in personnel time to dispense, administer and monitor patients.

Disadvantages of controlled-release dosage forms include —

1. Decreased systemic availability in comparison to immediate-release conventional dosage forms. This may be due to –

^·            Incomplete release

^·            Increased first-pass metabolism

^·            Increased instability

^·            Insufficient residence time for complete release

^·            Site-specific absorption

^·            pH-dependent solubility.

2. Poor in vitro–in vivo correlation.

3. Possibility of dose dumping due to food, physiologic or formulation variables or chewing or grinding of oral formulations by the patient and thus, increased risk of toxicity.

4. Retrieval of drug is difficult in case of toxicity, poisoning or hypersensitivity reactions.

5. Reduced potential for dosage adjustment of drugs normally administered in varying strengths.

6. Higher cost of formulation.