@article {46, title = {Hot-melt extrusion (HME)and its application for pharmacokinetic improvement of poorly water soluble drugs.}, journal = {Pharmacology, Toxicology and Biomedical Reports}, volume = {2}, year = {2016}, month = {August 2016}, pages = {47-51}, type = {Review Article}, chapter = {47}, abstract = {

For orally administered drugs solubility is one of the rate-limiting parameter to achieve their desired concentration in systemic circulation for pharmacological response. Poor solubility and poor permeability is responsible for 40 to 70\% incidence of delay or failure for new chemical entities during the developmental process. Due to this, formulation scientist faces a major challenge to develope a formulation with good bioavailability.By adopting various technological approaches during the pharmaceutical product development which include physical and chemical approaches such as micronization, pH adjustment, solid dispersion, complexation, co-solvent, salt formation, nanotechnology, use of surfactant, hydrotophy and polymorphs that can be overcome. At present due to its wide applications, simple process and low costs, solid dispersion prepared by hot melt extrusion (HME) has gained popularity in the pharmaceutical industry as a means of improving the bioavailability of drugs. Hot-melt extrusion (HME) is an efficient technology for producing solid molecular dispersions with considerable advantages including the absence of solvents, few processing steps, continuous operation over solvent-based processes such as spray drying and co-precipitation and HME is one of the recommonded process by FDA to encourage move from batch-to-continuous manufacturing.

}, keywords = {Absorption, Bioavailability, Hot melt extrusion, Poorly soluble drugs, Solid dispersion, Solubility}, doi = {10.5530/PTB.2016.2.7}, author = {Devendra Ridhurkar and Attila Vajdai and Zsolt Zsigmond} } @article {65, title = {The Importance of Pharmacokinetic and Pharmacodynamic Models in Sustained Release Formulation}, journal = {Pharmacology, Toxicology and Biomedical Reports}, volume = {1}, year = {2015}, month = {27th Feb, 2015}, pages = {5-9}, type = {Review Article}, chapter = {5}, abstract = {

The main role of preclinical pharmacokinetics and pharmacodynamics in drug discovery and development is to optimize candidate selection for the target therapeutic area, taking into consideration the type of agent required, and to predict the dose and dosing regimen for initial clinical trials with due concern to the requirements for effective treatment in the target therapeutic area. In order for this approach to be successful, a clear understanding is required for both the pharmacological target and drug disposition (absorption, clearance and distribution) of new chemical entities. A fundamental tenet in linking the pharmacokinetic and pharmacodynamic phases is that free drug in the systemic circulation is in equilibrium with the receptors. In the pharmacokinetic phase, only free drug can be cleared and drug is reversibly bound to tissues and blood. The pharmacodynamic phase is further subdivided into the interaction with the drug receptor triggering postreceptor events, eventually leading to actual drug effect. In this phase, only free drug can exert pharmacological effect and the free concentration of drug in plasma is in direct equilibrium with the interstitial fluid bathing most cells, since the capillary wall contains sufficient aqueous pores to allow the rapid passage of relatively small molecules, regardless of physicochemistry. Most receptor targets are accessed extracellularly. Therefore, one can expect that all drugs regardless of physicochemistry will be in direct equilibrium, at these targets, with free drug in plasma.

Key words: Bioavailability, Drug discovery, Formulations, PK-PD models, Sustained release dosage form.

}, keywords = {Bioavailability, Drug discovery, Formulations, PK-PD models, Sustained release dosage form.}, doi = {10.5530/PTB.1.1.3}, author = {Selvadurai Muralidharan and Kalaimani Jayaraja Kumar} }