The Pharmaceutics department is actively taking part in the following research activities:
Research in the Pharmaceutics Department encompasses basic, applied, and clinical investigations in
- Drug delivery
- Pharmacokinetics / Biopharmaceutics.
The major thrust area of pharmaceutics department is Drug delivery. Drug delivery is the method of administering an Active Pharmaceutical Ingredient (API) to achieve a therapeutic effect in humans or animals through various routes of adminstration. Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. The goal of drug formulation and delivery is to administer a drug at a therapeutic concentration to a particular site of action for a specified period of time. The design of the final formulated product for drug delivery is done by taking into consideration the physical, chemical and pharmacokinetic and dynamic properties of the drug substance, the route of administration, the processing method and the clinical use of the product.
Current efforts in the area of drug delivery include the development of formulations that includes Immediate Release systems, Modified drug delivery systems including Novel Drug Delivery Systems (NDDS), Targeted Drug Delivery systems.
The training and research activity for first semester students involve in the areas of solubility improvement techniques, solid state manipulation, improvement in dissolution, IR dosage form development, NDDS formulation and evaluation like TDDS, niosomes, gels, matrix and coated particulate systems.
IMPROVING THE BIOAVAILABILITY OF POORLY SOLUBLE DRUGS
More than 40% of drugs released in recent years have very low aqueous solubilities and also low and/or varying bioavailabilities. Many are Class 2 substances according to the Biopharmaceutical Classification System, meaning that they have a high permeability, and that the solubilization in the gastro-intestinal (GI) tract is the rate limiting step for their absorption. Solubilization in the GI tract will depend on physico-chemical properties of the drug substance (e.g. solubility and particle size) as well as physiological factors (e.g. composition, volume and hydrodynamics) of the GI fluids. The physical and chemical properties of the GI tract are complex and strongly dependent on nutritional status. Since the absorption of class 2 drugs is primarily limited by dissolution, a correlation between in vitro dissolution and in vivo absorption might be expected.
Presently our department is working on the improvement of bioavailablity of BCS class II drugs with the aid of solubility enhancement methods like cosolvency, micellization, complexation, Lipid-based formulations and use of mesoporous silica for adsorption of these drugs
ORAL DISINTEGRATING EXTENDED RELEASE FORMULATIONS FOR GERIATRICS AND PEDIATRICS
Oral disintegrating extended release formulation can reduce the adverse effect caused by the fluctuating plasma drug concentration and also increases the compliance of geriatric patients. Oral modified release multiparticulate systems offer better option in comparison to conventional or immediate single unit dosage form. The multiparticulate systems are usually filled into the capsules or compressed into tablets. The main problem with the capsule formulation is their low production rate and high cost, which make the tablet more promising system for multiparticulate system. However, the compression of coated particles is a challenging process and requires optimization of number of parameters like coating of cores, coating material and coating thickness, cushioning materials, etc. Other advantages of the multiparticulate systems are reduction in dose dumping, tamper proof and reduction in the GI irritation. Research work has been initiated in this area to formulated compressed rapid release multiparticulate systems for class I and class II drugs.
NANOSTRUCTURED LIPID CARRIERS FOR TOPICAL DELIVERY
The department has commenced a project focused on NDDS like, Nanostructured lipid carrier (NLC) a new generation type of solid lipid nanoparticles for delivering antifungal drugs like, Itraconazole. NLC is composed of solid lipid matrix and liquid lipid in the ratio of 70:30 and it can be up to 99.9:0.1. The mean particle size of the carrier system is in the submicron range, ranging from about 40 nm to 1000 nm. Drug loaded Nanostructured lipid carrier and incorporated into gels for convenient topical application and will be evaluated for ex vivo skin penetration. Stratum corneum is the main barrier in the percutaneous absorption of topically applied drugs. Small size and relatively narrow size distribution of drug loaded NLC permit site-specific delivery of drug to the skin.
PLASMA PROTEIN BINDING STUDIES
The pharmacokinetic and pharmacodynamic properties of drugs are largely a function of the reversible binding of drugs to plasma or serum proteins. Such proteins include albumin, α1-acid glycoprotein, lipoproteins and α, ß‚ and γ globulins. Generally, only the unbound drug is available for diffusion or transport across cell membranes, and for interaction with a pharmacological target (e.g. receptor, ion channel, transporter, and enzyme). As a result, the extent of plasma protein binding of a drug influences the drug’s action as well as its distribution and elimination. A thorough understanding of plasma and tissue (brain, liver, etc.) protein binding is crucial for evaluating the distribution of drug candidates.
Highly plasma protein bound drugs are confined to the vascular space, thereby having a relatively low volume of distribution. In contrast, drugs that remain largely unbound in plasma are generally available for distribution to other organs and tissues, resulting in large volumes of distribution. The binding of drugs to proteins both in the vascular space and/or the extravascular space results in a decrease in drug clearance and a prolonged drug half-life. Only the unbound drug is available for glomerular filtration and, in some cases, hepatic clearance. However, for high extraction ratio drugs, clearance is relatively independent of protein binding.
IN-VITRO METABOLISM AND DISTRIBUTION STUDIES OF ENANTIOMERS
About 50% of therapeutic drugs are currently administered as a racemate, a mixture of equal proportions of two enantiomers. In an achiral environment, the enantiomers of a chiral drug show identical chemical and physical properties. However, they can present different chemical and pharmacological behavior in a chiral environment such as in the body. The interaction of two enantiomers with a chiral macromolecule, such as an enzyme or receptor, is three dimensional in nature, forming diastereomeric complexes resulting in a chiral recognition process. Moreover, when administered as a racemate, two enantiomers can display the pharmacokinetic processes (absorption, distribution, metabolism and excretion) in a stereoselective manner. Among these processes, stereoselectivity plays a central role in the metabolism due to the involvement of the enzymatic system.The purpose of this study is to evaluate the invitro metabolism and distribution of Rasagiline enantiomers and contribution of various cytochrome P450 isoforms to enantioselective metabolism.