Biomedical subjects

Venkatramana M Rao

Publications and source records attributed to Venkatramana M Rao.

3 recordsLinked to original sources

PubMed2006

Co-solubilization of poorly soluble drugs by micellization and complexation.

The use of combined approach of surfactants and cyclodextrins in solubilization of poorly soluble drugs has been described in literature. In this report, a mathematical model has been developed to provide the quantitative basis for this approach. First, by way of hypothetical examples and simulations, the influence of various interaction parameters on the phase solubility profile is presented. Additionally, the model results are compared with (a) results reported by Yang et al., with NSC-639829, sodium lauryl sulfate (SLS) and sulfobutyl-ether-beta-cyclodextrin ((SBE)(7M)-beta-CD) and (b) solubility of methylprednisolone, a model poorly soluble drug, in the presence of its water-soluble 'surfactant-like' prodrug, methylprednisolone 21-hemisuccinate, and (SBE)(7M)-beta-CD. The model shows good agreement with experimental data. Furthermore, theoretical simulations show that the combined solubility is less than the sum of the individual solubility values in cyclodextrins and surfactants. Based on the hypothetical case and the two examples, the factors affecting the phase solubility profile in mixed solutions of surfactants and cyclodextrins are presented. Finally, the limitations of the model to explain co-solubilization by surfactants and cyclodextrins are discussed.

Chemistry, Pharmaceutical↗

PubMed2003

Design of pH-independent controlled release matrix tablets for acidic drugs.

The rate and extent of drug release from most controlled release systems are influenced by the pH of the dissolution medium for drugs with pH-dependent solubility. This dependency of drug release on pH may lead to additional inter- and intra-subject variability in drug absorption. In the present study, a pH-independent controlled release matrix system for acidic drugs was designed by incorporating release-modifiers in the formulation. Controlled release matrix tablets were prepared by compression of divalproex sodium, Methocel K4M and Eudragit E 100 or Fujicalin as the release-modifier. For formulations without any release-modifier, the extent and rate of drug release at pH 6.8 was much higher than that at pH 1.0. Formulations containing Eudragit E 100 provided drug release that was essentially independent of pH. This was achieved because Eudragit E 100 significantly increased the drug release in acidic medium and slightly decreased the release rate at higher pH. The increased release in the acidic medium can be attributed to the elevation of the micro-environmental pH in the swollen polymer gel layer. Formulations containing Fujicalin were less effective than those containing Eudragit E 100. This was attributed to the relative inability to elevate the pH and shorter residence time of Fujicalin in the matrix relative to Eudragit E 100.

Delayed-Action Preparations↗

PubMed2003

When can cyclodextrins be considered for solubilization purposes?

This communication is intended to address the question: How can one determine, with minimum experimentation, if cyclodextrins (CDs) might be the right choice as solubilization enhancers for a given poorly water-soluble drug? The cyclodextrin utility number, U(CD), a dimensionless number, is introduced to assess the feasibility of the use of CDs in dosage forms. U(CD) is a lumped-parameter consisting of the dose of the drug, the workable amount of CD, the binding constant, and the drug solubility in the absence of CDs. U(CD) was been extended to ionizable drugs that show synergistic increase in solubility due to ionization and complexation. U(CD) is a guiding and not a predictive tool that the formulator can use.

Chemistry, Pharmaceutical↗