Formulation and Evaluation of Oxcarbazepine Suspension: In vitro/In vivo Correlation.

Aims: Oxcarbazepine was formulated as suspension in order to perk up the palatability, augment bioavailability of the product, furthermore extended to estimate good degree of in vitro in vivo correlation (IVIVC). Study Design: Formulation and Evaluation of Oxcarbazepine Suspension: In Vitro/In Vivo Correlation Place and Duration of Study: Birla Institute of Technological Sciences- Hyderabad, India between July 2011 to January 2012 Methodology: Oxcarbazepine had poor aqueous solubility, thus the solubility was increased by hydrotropes then formulated into suspension using taragum as viscosity enhancer. Further validity of dissolution study was extended by In vitro/In vivo correlation using level A method. Results: These suspensions were observed for in vitro dissolution profile and studied for in vivo pharmacokinetic profile, from the obtained values, a level A IVIVC modeling was observed, interestingly from the results attained suspension showed almost 98% drug release (FDR) and 85% drug absorbed (FDA) in 90min. Fascinatingly, from the correlation between FDR and FDA, slope and regression co-efficient obtained was near to 1.0 indicated good linearity. Conclusion: In conclusion, a point-to-point link from the level A which was a keystone of acceptable and reliable correlation was achieved.

Extrapolated response dose as a potential tool in radiotherapy and chemo-radiotherapy of head and neck cancers.

An analysis of head and neck cancer patients treated by radiotherapy (RT) alone (114 patients) and by chemo-radiotherapy (RT + CT) (115 patients) was carried out; the doses varied from 40-77 Gy and 35-71 Gy in RT and RT + CT groups respectively. The chemotherapy (CT) (induction/concurrent) drugs used were 5-FU, cisplatin, methotrexate either single or in combination. Extrapolated response dose values were evaluated with alpha/beta values of 10, 2.5 and 6 Gy for acute, late complications and tumour response, respectively. Dose enhancement factor (DEF) and Therapeutic gain factor (TGF) values were evaluated on the basis of ERD for patients receiving 5-FU RTCT (72 patients). ERD vs late complication rate and response rate curves were drawn for RT, RT + CT (< 7 cycles), RT + CT (> 6 cycles) and RT + CT (cumulative). DEF values for response rate were 0.95, 0.95 and 0.82 for the three RT + CT groups respectively. Similarly DEF values for late complication rate were evaluated as 0.87, 0.93 and 0.88. TGF values for RT + CT were 1.09, 1.02 and 0.93. TGF values indicated lack of significant influence of CT on clinical outcome. The correlation of ERD with late complication, response and status at last follow up (NED) was statistically significant for both groups (P < 0.01). ERD did not correlated with acute complication in RT group (P > 0.01). From the present analysis, in RT + CT treatments of head and neck cancers, an ERD value of 69 Gy is suggested as the limit for an acceptable 5% late complication rate.