Biomedical subjects

T R Shantha Kumar

Publications and source records attributed to T R Shantha Kumar.

4 recordsLinked to original sources

PubMed2006

High-performance liquid chromatography method development and validation for simultaneous determination of five model compounds, antipyrine, metoprolol, ketoprofen, furosemide and phenol red, as a tool for the standardization of rat in situ intestinal permeability studies using timed wavelength detection.

A simple, precise, accurate and rugged reversed-phase high-performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of five permeability model compounds, viz. antipyrine, metoprolol, ketoprofen, furosemide and phenol red. The method was intended to standardize rat in situ single-pass intestinal perfusion studies to assess the intestinal permeability of drugs in the market as well as new chemical entities. Optimum resolution was achieved by gradient elution on a Symmetry Shield C-18 analytical column with the mobile phase consisting of a mixture of aqueous potassium dihydrogen orthophosphate (pH 5.5; 0.01 m) and methanol at a flow rate of 1.5 mL/min. The retention times of antipyrine, metoprolol, ketoprofen, phenol red and furosemide were about 9, 12, 13, 16 and 17 min, respectively. Data acquisition was carried out using a photo diode array detector in the wavelength range 210-600 nm. Extraction of chromatograms was carried out by timed wavelength. Data obtained in all studies indicated that the method was suitable for the intended purpose. The validated method was found to be linear and precise in the working range. Suitability of storage under various conditions and freeze/thaw impact at cold temperature were established to ensure complete sample recovery without any stability issues. Recovery very close to the spiked amounts indicated that the method was highly accurate and suitable for use on routine basis.

Animals↗

PubMed2006

Bioavailability enhancement of poorly water soluble and weakly acidic new chemical entity with 2-hydroxy propyl-beta-cyclodextrin: selection of meglumine, a polyhydroxy base, as a novel ternary component.

The purpose of the present study was to investigate the influence of a polyhydroxy base, N-acetyl glucamine (also know as Meglumine), as a ternary component on the complexation of DRF-4367, a poorly water-soluble and weakly acidic anti-inflammatory molecule, with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). The molecular inclusion of DRF-4367 with HPbetaCD alone and in combination with ternary component was aimed at improvement in solubility and, subsequently, dissolution rate-limited oral bioavailability. The solid complexes of DRF-4367 and HPbetaCD with or without meglumine (binary and ternary systems, respectively) were prepared as coevaporated product in different stoichiometric ratios and compared against physical mixture. The formation of inclusion complexes was confirmed by using classical instrumental techniques. Phase solubility studies suggested that meglumine was responsible for solubility improvement via multiple factors rather than just providing a favorable pH. Mechanisms and factors governing solubility enhancement were investigated by using phase solubility and thermodynamic parameters. The complexation of DRF-4367 with HPbetaCD is thermodynamically favored because the Gibbs free energies of transfer of the drug to the cyclodextrin cavity are negative. The solubilization efficiency and stability were further improved while retaining the favorable Gibbs free energies of transfer with the addition of meglumine. Inclusion ternary complex of DRF-4367 with HPbetaCD and meglumine showed significant improvement in dissolution compared with uncomplexed drug and binary system. Moreover, the phenomena of reprecipitation observed with binary system during dissolution could be avoided with meglumine as an enabling ternary component. This improved physicochemical behavior of ternary complex with the novel inclusion of a polyhydroxy base translated into an enhanced oral bioavailability of DRF-4367 compared with either uncomplexed drug or nanosuspension.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2006

Novel delivery technologies for protein and peptide therapeutics.

The protein and peptide therapeutics have become an important class of drugs due to advancement in molecular biology and recombinant technology. There are more than 100 biopharmaceutical products approved and generating revenue of more than 56 billion US dollars. A safe, effective and patient friendly delivery of these agents is the key to commercial success. Currently, most of therapeutic proteins are administered by the parenteral route which has many drawbacks. Various delivery strategies and specialized companies have evolved over the past few years to improve delivery of proteins and peptides. Polymeric depot and PEGylation technologies have overcome some of the issues associated with parenteral delivery. A considerable research has been focused on non-invasive routes such as pulmonary, per oral and transdermal for delivery of proteins and peptides, in order to increase patient compliance yet their delivery via non-invasive routes remains challenge due to their poor absorption and enzymatic instability. Pulmonary route has shown some success evidenced by recent FDA approval of inhalable insulin. Development of an oral dosage form for protein therapeutics is still the most desirable one but with greater challenge. This review presents the issues of delivery of proteins and peptides, current and potential formulation technologies to improve delivery and current market trends.

Administration, Oral↗

PubMed2005

Validated HPLC analytical method with programmed wavelength UV detection for simultaneous determination of DRF-4367 and Phenol red in rat in situ intestinal perfusion study.

A simple, precise and accurate isocratic reverse-phase liquid chromatography method with programmed wavelength detection has been validated to quantify DRF-4367 and Phenol red, simultaneously for application in rat in situ single pass intestinal perfusion study to assess intestinal permeability of DRF-4367, a novel cox-2 inhibitor. The method was validated on RP C-18 analytical column. Mobile phase consisted of sodium dihydrogen orthophosphate (pH 3.2, 0.01 M)-acetonitrile-methanol (30:50:20, v/v/v). The developed method has a short run time of 12 min with a flow rate of 1.0 ml/min. The injector volume was set to 20 microl and acquisition was carried out using a PDA detector while processing was done by timed wavelength extraction. The percentage R.S.D. and recovery in all studies indicated that the method was suitable for the intended purpose. The validated method was found to be linear and precise in the working range. Suitability of storage at cold temperature was ensured along with complete sample recovery.

Animals↗