Pharma Nueva is a Contract Research Organization (CRO) with an expertise on pharmaceutical and related fields. We offer a full range of services that can add value to any pharmaceutical/ nutraceutical researches from project conception to documentation for submission to regulatory authorities.

 

If you are interested in our services on formulation development, analytical testing, stability study, method development and method validation, you can contact through 3 ways i.e., e-mail: service@pharmanueva.com, Tel.: +66 2 625 9696 or +66 2 625 9697 and
Fax: +66 2 276 1543.
 

Polymorphism is the ability of drug substance to exist in different crystal structures. Polymorphs of a pharmaceutical solid can have different chemical and physical properties such as melting point, chemical reactivity, apparent solubility, dissolution rate, optical and electrical properties, vapor pressure and density.

Reference: http://www.fda.gov/ohrms/dockets/ac/02/briefing/3900B1_04_Polymorphism.htm
 

Polymorphism of drug substances has a crucial impact on physical properties of the substances, i.e. solubility, thermal properties, stability, resulting in great differences in dissolution rate and stability of the solid dosage forms. Additionally, this would have a consequent effect on bioavailability of the drug after oral administration. The issue is therefore concerned in the pharmaceutical development process.
 

Many techniques are commonly applied to characterize polymorphism, for examples, melting point, solid state IR, X-ray powder diffraction, thermal analysis procedures (DSC, TGA and DTA), Raman spectroscopy, optical microscopy, and solid state NMR.

Reference: ICH Q6A. (1999). Specifications: Test procedures and acceptance criteria for new drug substances and new drug products.

 

ICH guideline Q3A (R2) and Q3B (R2) is the most frequently applied.
 

Bioanalytical development involves with pharmacokinetic and bioequivalence studies including analysis of drug substances in biological matrix and method validation.

Biological matrix is a discrete material of biological origin that can be sampled i.e. blood, serum, plasma, urine, feces, saliva, sputum, and various discrete tissues.

Bioequivalence is a term in the determination of statistical indifference between two products such as a commercially available Brand product as a reference product and a potentially possible marketed Generic product in aspect of equivalent pharmacokinetic parameters i.e. C_max and AUC.
 

A bioequivalence study is an experiment which shows the equivalence in terms of pharmacokinetic parameters i.e. C_max, AUC_(0-t) and AUC_(0-oo) between two pharmaceutical products. Generally, the US FDA considers two products bioequivalent if the 90% CI of the relative mean C_max, AUC_(0-t) and AUC_(0-oo) of test product (Generic formulation) to reference product (Brand formulation) should be within 80.00% to 125.00% in the fasting state.

 

There are several information needed to be declared before bioequivalence study initiation. Pharmaceutical equivalence study should be first verified to prove the identical quality of the test and reference product. Additionally, method validation of the bioanalytical determination is important information to guarantee the accuracy, precision, selectivity and specificity of the method involved in the analysis.
 

Pharmaceutical equivalence test is a study to prove the identical quality of the test and reference in drug assay, uniformity of content, and dissolution profiles in the specified dissolution media. These results not only confirm the pharmaceutically identical aspects between the test and reference products, but also ensure the safety issue of the test product before performing the bioequivalence study in healthy volunteers.
 

US and EMA guidance are the two most frequently guidance applied in the method validation. Additionally, EMA and Asean guidance are also accepted by Thai FDA to be used as a standard guideline for bioequivalence study.