Controlling Drug Release Through Osmotic Systems - Pharmaceutical Technology

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Controlling Drug Release Through Osmotic Systems
Osmotic systems offer versatility for delivering drugs with varied properties and dosage requirements.

Pharmaceutical Technology
Volume 37, Issue 7, pp. 40-44

Basic components
Osmotic systems essentially contain a drug and a semipermeable membrane. Ideal candidates for these systems are drugs with short biological half-life, which require prolonged treatment, such as drugs for hypertension (e.g., nifedipine) or diabetes (e.g., glipizide) (12).

Drugs with good water solubility may act as an osmotic agent or osmogen that draws water into the osmotic core. However, if the drug does not possess osmogenic properties, osmogenic salts (e.g., sodium chloride and potassium chloride) and sugars can be incorporated into the formulation (11). When selecting an osmogen, the two most important properties to consider are water solubility and osmotic activity.

The semipermeable membrane is an important component because it controls the rate of water influx into the drug core as well as retains water-soluble components within the core to create the osmotic pressure gradient that drives the osmotic system (9). The semipermeable membrane must possess certain performance criteria, such as sufficient wet strength and water permeability, and should be selectively permeable to water and biocompatible (13). Cellulose acetate, a water-insoluble film-forming polymer, is commonly used in osmotic systems. Release rate is affected by the molecular weight and acetyl content of the various grades of cellulose acetate. The semipermeable membrane usually contains a plasticizer, which moderates the permeability of the membrane, and in some cases, surfactants, flux regulators and pore-forming agents (11).

Formulation factors affecting drug release
Key parameters (i.e., drug solubility, osmotic pressure, the size of the delivery orifice and semipermeable membrane) that influence the design of osmotically controlled drug-delivery systems are briefly summarized.

Drug solubility: To achieve optimized drug release, the API for osmotic delivery should have sufficient water solubility, given that the release rate is directly proportional to the solubility of the API within the core. Drugs with extremes of solubility are generally poor candidates for osmotic delivery. There are, however, approaches to modify the solubility of such drugs within the core so that the desired release patterns can be attained.

For compounds with low solubility, solubilizing strategies can be employed; for example, by using alternative salt forms or cyclodextrins. Swellable polymers (e.g., vinyl acetate copolymer and polyethylene oxide) can also be added; the uniform swelling of these polymers facilitates drug release at a constant rate. Wicking agents help to increase the contact surface area of the drug with incoming fluids. The use of wicking agents can help enhance the rate of drug release from the orifice of the osmotic system (12, 14).

Osmotic pressure: The osmotic pressure gradient between the drug core of the osmotic system and the external environment is another important factor that controls drug release, with release rate being directly proportional to the osmotic pressure of the core. The simplest and most predictive way to achieve constant osmotic pressure would be to maintain a saturated solution of osmotic agent in the drug-core compartment (3).

Size of the delivery orifice: The size of the orifice must be within a certain range for controlled release. The typical range is 0.5 mm to 1.0 mm in diameter (9). For an optimal zero-order delivery profile, the cross-sectional area of the orifice must be small enough to minimize drug passage through the orifice but large enough to minimize the build-up of hydrostatic pressure within the osmotic system (14). The orifice can be created by using a mechanical drill or by laser drilling, which is now a well-established technology that offers reliability at low costs. Other methods to create an orifice are by indentation with modified punches that have a needle on the upper punch or by using leachable substances in the semipermeable coating (13).

Semipermeable membrane: Drug release rate is affected by the type and nature of the membrane-forming polymer used, membrane thickness, and the presence of other additives (e.g., type and nature of plasticizers used). Membrane permeability can be increased or decreased by the proper choice of membrane-forming polymers and other additives (3).


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