Enhancement of solubility and oral bioavailability of poorly soluble drugs – A Review
Drug solubility can pose a great challenge for the development of novel formulations and impacts a wide spectrum of drugs with poor solubilities. Drug efficacy is known to be proportionally related to the solubility of a drug. Poor solubility of a drug leads to low dissolution rate and in turn to low absorption in the gastrointestinal tract following oral administration. Pharmaceutical particle technology is often used to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids after oral administration. This review discusses various particle techniques employed for improving the solubility of poorly water soluble drugs. The particle technology involves several approaches from the conventional size reduction processes to the newer novel approaches. The conventional methods of size reduction involve mechanical micronization techniques that are simple and convenient methods to reduce drug particle size and increase the surface area and thus enhance the solubility of poorly soluble drugs. The conventional particle technologies pose limitations for some drugs due to their low efficiency hence novel particle technologies are used to overcome these issues of the conventional methods. Novel particle technologies modify the solubility properties of the drugs and produce a solid, powdered form of the drug that is easily soluble in aqueous media and can be formulated into various dosage forms without difficulties.
For orally administered drugs, solubility is one of the rate limiting parameters to achieve their desired concentration in systemic circulation for pharmacological response. Drug solubility is the key factor that impacts the formulation and therapeutic efficacy of the drug. These particle size reduction technologies can be divided into two main categories: Conventional methods and the Novel approaches. The conventional size reduction techniques are simple and convenient methods that offer increase the surface area by the reduction of the drug particle size. Novel techniques include the basic particle size reduction principles but overcome many of the obstacles and limitations used with conventional methods.
Various techniques described in this review may be used alone or in combination with other to enhance the solubility of poorly aqueous soluble drugs. Selection of a solubility enhancement technique is important to meet critical formulation attribites such as: good oral bioavailability, reduced dosing frequency, and better patient compliance, with a relatively low production cost. The method for selecting an appropriate solubility enhancement technique is dependant on drug characteristics including: solubility, chemical nature, melting point, absorption site, physical nature, pharmacokinetic behavior, dosage form requirements (tablets or capsules), drug loading, immediate or modified release, and maximum daily dose, regulatory, approved excipients, and analytical quantitation methods. Solubility enhancement of poorly solubility drugs is a challange and many drugs are affected to their bioavailability. Recent advancements in processing technolgoies have now made it possible to increase the solubility of poorly soluble drugs with the various techniques as described in this review article better than before.
aErnest Mario School of Pharmacy, Rutgers — The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
bCenter for Dermal Research, Rutgers — The State University of New Jersey, 145 Bevier Rd, Piscataway, NJ 08854, USA.
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