The design and development of controlled-release drug-delivery systems have been traditionally used to extend a product's lifecycle, for example, by modifying an existing drug product that requires multiple dosing a day to a once-daily formulation to maintain dominance over generic competition (1, 2). While this rationale still holds true today, the number of compounds formulated into controlled-release systems are increasing because of their added value and well-recognized advantages such as improved systemic bioavailability, more favorable pharmacokinetic profiles (e.g., the maintenance of drug levels within a desired range without exposing patients to potentially toxic or subtherapeutic levels), reduced side effects, and better patient compliance among others (3–5). From a strategic perspective, commercial and industrial advantages of controlled-release drug delivery, apart from prolonging product lifecycle, include patent extension, market expansion, and product differentiation (6, 7).
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Controlled-release technologies play a vital role in today's current healthcare market, given the strong emphasis placed on product value and cost effectiveness. Treatment of many diseases requires a dosage regimen that delivers acceptable therapeutic concentrations of the drug at the site of action, which can be attained immediately and then constantly maintained over the desired duration of treatment (8). Controlled-release drug delivery offers solutions to conventional problems of drug administration by regulating the patterns of drug release and absorption as well as the localization of therapeutic agents. The maintenance of stable drug levels in the plasma over a defined and extended period, achieved with controlled-release systems, minimizes peak-to-trough variations of drug concentration in the systemic circulation and allows dosing frequency to be reduced, thereby improving patient compliance and overall clinical utility (1, 6). There are, however, potential disadvantages of controlled-release systems that should not be overlooked, such as dose dumping, possible toxicity or nonbiocompatibility of the materials used, undesirable by-products of degradation, higher manufacturing costs, and for implants, the requirement of surgical procedures to insert or remove these systems as well as possible patient discomfort from the delivery device (4, 5).
Osmotically controlled oral drug-delivery systems
Osmotically controlled oral drug-delivery systems have gained popularity because of the following advantages over other controlled-release strategies (9, 11, 12):
One way to control drug release is by using osmotic systems, which operate on the principles of osmosis (i.e., the movement of solvent through a semipermeable membrane into a region of higher solute concentration until the solute concentrations are equal on both sides of the membrane). Osmotic systems consist of a drug core contained within a semipermeable polymer membrane that is permeable to water molecules but not to the drug, with an orifice for drug delivery. Drug release is driven by the osmotic pressure generated within the drug core upon exposure to water and is, to a large extent, independent of physiological factors (9, 10). Release characteristics can be modulated by optimizing the properties of both the drug and system (4).
- Zero-order kinetic release is achievable.
- The drug is delivered at a constant rate that is independent of time and drug concentration.
- The release rate is highly predictable.
- Higher release rates are possible compared with conventional drug-delivery systems.
- Drug release is independent of physiological factors of the gastrointestinal tract, including gastric pH and hydrodynamic conditions.
- Drug release is generally not affected by the presence of food.
- The release rate can be programmed by modulating release-control parameters.
- Delivery may be delayed or pulsed if desired.
- There is a high degree of in vivo-in vitro correlation.
- Soluble and insoluble compounds can be delivered.
- Production scale-up is easy.