Tuning solubility and stability of hydrochlorothiazide co-crystals

Hydrochlorothiazide (HCT), C7H8ClN3O4S2, is a diuretic BCS (Biopharmaceutics Classification System) class IV drug which has primary and secondary sulfonamide groups. To modify the aqueous solubility of the drug, co-crystals with biologically safe co-formers were screened. Multi-component molecular crystals of HCT were prepared with nicotinic acid, nicotinamide, succinamide, p-aminobenzoic acid, resorcinol and pyrogallol using liquid-assisted grinding. The co-crystals were characterized by FT-IR spectroscopy, powder X-ray diffraction (PXRD) and differential scanning calorimetry. Single crystal structures were obtained for four of them. The N-H center dot center dot center dot O sulfonamide catemer synthons found in the stable polymorph of pure HCT are replaced in the co-crystals by drug-co-former heterosynthons. Isostructural co-crystals with nicotinic acid and nicotinamide are devoid of the common sulfonamide dimer/catemer synthons. Solubility and stability experiments were carried out for the co-crystals in water (neutral pH) under ambient conditions. Among the six binary systems, the co-crystal with p-aminobenzoic acid showed a sixfold increase in solubility compared with pure HCT, and stability up to 24 h in an aqueous medium. The co-crystals with nicotinamide, resorcinol and pyrogallol showed only a 1.5-2-fold increase in solubility and transformed to HCT within 1 h of the dissolution experiment. An inverse correlation is observed between the melting points of the co-crystals and their solubilities.

State estimation of spiralling target using UKF with generalized sinusoidal target acceleration model

Hit-to-kill interception of high velocity spiraling target requires accurate state estimation of relative kinematic parameters describing spiralling motion. In this pa- per, spiraling target motion is captured by representing target acceleration through sinusoidal function in inertial frame. A nine state unscented Kalman filter (UKF) formulation is presented here with three relative positions, three relative velocities, spiraling frequency of target, inverse of ballistic coefficient and maneuvering coef-ficient. A key advantage of the target model presented here is that it is of generic nature and can capture spiraling as well as pure ballistic motions without any change of tuning parameters. Extensive Six-DOF simulation experiments, which includes a modified PN guidance and dynamic inversion based autopilot, show that near Hit-to-Kill performance can be obtained with noisy RF seeker measurements of gimbal angles, gimbal angle rates, range and range rate.