Development Of Water Transplant Based Single Core Osmotic Pump For Fluvoxamine Maleate Employing Quality By Design Principles

The present study draw a bead on preparing single core osmotic pump with improved water transplant by employing Quality by Design (QbD) principles to achieve zero order drug release for prolonged period of time. QbD principles were employed in preparing single core osmotic pump by deriving quality target product profile (QTPP), critical quality attributes (CQA) followed by risk assessment using ishikawa diagram and risk estimation matrix. Box-Behnken Design was employed to study the effect of various independent parameters like concentration of Natrosol 250 HX (X1) and concentration of Xylitab (X2) no. of orifice (X3), on various dependent parameters like lag time (Y1) and time required for release 25%, 50%, 75% and 100% drug (Y2, Y3, Y4 and Y5). A controlled space was designed where each criteria or CQA was satisfied. Optimized formulation was further characterized for its efficiency. The results of design suggest the suitability of design for optimization of single core osmotic pump. In the initial period, drug release was driven by no. of orifice which on later stage depends on concentration of swellable polymer and concentration of osmogen. Optimized design was validated by preparing check point batch having less than 5% predicted error. Model fitting with drug release kinetics showed that optimized single core osmotic pump released drug in zero order. Stability data suggested that prepared formulation was stable for 3 month period without significant changes in the CQA. Single core osmotic pump using water transplant was successfully developed for a poorly soluble drug using QbD principles.

New Spectrophotometric Methods for Simultaneous Determination of Amlodipine besylate and Lisinopril in Tablet Dosage Forms.

Two simple, accurate, precise, reproducible, requiring no prior separation and economical procedures for simultaneous estimation of Amlodipine besylate (AML) and Lisinopril (LIS) in tablet dosage form have been developed. First method is simultaneous equation method; in this method 360.0 nm and 248.0 nm were selected to measure the absorbance of drugs at both wavelengths. The second method is Q-value analysis based on measurement of absorptivity at 300.0 nm (as an iso-absorptive point) and 360.0 nm. AMD and LIS at maximum wavelength of AML, 360.0 nm and at isoabsorptive point 300.0 nm shows linearity in a concentration range of 5- 40 μg/mL. Recovery studies range from >99.82% for AMD and >98.09% for LIS in case of simultaneous equation method and >100% for AMD and >98.45% for LIS in case of Q-analysis method confirming the accuracy of the proposed method. The proposed methods are recommended for routine analysis since it is rapid, simple, accurate and also sensitive and specific (no heating and no organic solvent extraction is required).

Nucleolar organizer region heteromorphism associated with trisomy-21: a risk factor for non-disjunction?

An unusual nucleolar organizer region (double NOR) on chromosome 13 was observed in a Down syndrome child [47, XY, +21, dNOR(13)]. The variant chromosome was inherited from the mother [46, XX, dNOR(13)]. The extra chromosome 21 in the proband was maternal origin. The frequency of NOR chromosome association showed relatively high frequency in the mother and proband as compared to the controls. The result suggest that chromosome variants involving extra copies of NOR may indeed be involved in the meiotic nondisjunction of chromosome-21.

Correlation of fragile sites and bleomycin induced chromosome break points.

Bleomycin (Blm) induced break points in human chromosome preparations were compared with the known fragile sites. A total of 136 breaks were observed from 100 well spread G-banded plates (1.3 bps/cell). These correspond to a total of 57 break prone sites. Of these 57 sites, 24 correspond to the known fragile sites, 5 to sites of protooncogenes and neoplasia, 26 sites correspond to more than one known site of fragility, protooncogene, neoplasia or reciprocal translocation sites, and 2 unknown sites. The findings suggest that fragile sites, either commonly expressed or induced, might be a predisposing factor for chromosome aberrations in human. The expression of fragile sites induced by Blm and their correlation with the known cancer chromosome break points, oncogenes and reciprocal translocation, suggest that the fragile sites are prone to mutagenic action.