DPC 963 is a non-nucleoside reverse transcriptase inhibitor with low aqueous solubility.
Solubility Enhancement: REDUCTION OF DRUG PARTICLE SIZE
As a continuation to the previous blog, we are discussing the individual methods in detail. Actually it was not planned but after getting such response & queries from reader it came like that,
REDUCTION OF DRUG PARTICLE SIZE:
• The bioavailability: intrinsically related to drug particle size.
• Increased surface area improves the dissolution properties.
• Achieved by micronisation & nanosuspension.
• Increases the dissolution rate of drugs through increased surface area; it does not increase equilibrium solubility.
• Done by milling techniques using jet mill, rotor stator colloid mills etc.
• Not suitable for drugs having a high dose number because it does not change the saturation solubility of the drug
• Nanosuspensions are sub-micron colloidal dispersion of pure particles of drug, which are stabilised by surfactants.
• Increased dissolution rate is due to larger surface area exposed, while absence of Ostwald ripening is due to the uniform and narrow particle size range obtained, which eliminates the concentration gradient factor.
• The nanosuspension approach has been employed for drugs including tarazepide, atovaquone, amphotericin B, paclitaxel and bupravaquone
• Techniques for the production of nanosuspensions
• Homogenization: The suspension is forced under pressure through a valve that has nano aperture. This causes bubbles of water to form which collapses as they come out of valves. This mechanism cracks the particles. Conventional homogenizers, sonicators, and high shear fluid processors.
• Wet milling: Active drug in the presence of surfactant is defragmented by milling. Other technique involves the spraying of a drug solution in a volatile organic solvent into a heated aqueous solution. Rapid solvent evaporation produces drug precipitation in the presence of surfactants.
• Other techniques for reduction of the particle size
– Sonocrystallisation: Recrystallization of poorly soluble materials using liquid solvents and antisolvents. By using ultrasound is Sonocrystallisation. Sonocrystallisation utilizes ultrasound power characterised by a frequency range of 20–100 kHz for inducing crystallisation. It’s not only enhances the nucleation rate but also an effective means of size reduction and controlling size distribution of the API. Most applications use ultrasound in the range 20 kHz-5 MHz. Supercritical fluid process
– Spray drying: Drying a liquid feed through a hot gas. The liquid feed varies depending on the material being dried and is not limited to food or pharmaceutical products and may be a solution, colloid or a suspension. This process of drying is a one step rapid process and eliminates additional processing. Spray drying of the acid dispersed in acacia solutions resulted in as much as a 50% improvement in the solubility of poorly water soluble salicylic acid.
– Supercritical Fluid Process: SCF process allows micronisation of drug particles within narrow range of particle size, often to sub-micron levels. Current SCF processes have demonstrated the ability to create nanoparticulate suspensions of particles 5 to 2,000 nm in diameter.
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