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Schizophrenia and bipolar disorder stand as intense and persistent mental illnesses. This research underscores the development of a niosomal thermoreversible gel for intranasal drug delivery with a focus on precise administration to the olfactory lobe. Utilizing a 32 factorial design, lurasidone hydrochloride niosomes were fabricated through the thin film hydration method. The niosomes underwent assessment to determine their encapsulation efficiency, particle size, zeta potential and polydispersity index whereas thermoreversible niosomal in situ gel based on PF-127 in conjunction with HPMC K4M was characterized for pH, gelation time, temperature responsiveness, in vitro release and rheological characteristics. The results indicated that the optimized batch (F4) illustrated a particle size of 171.4 ± 5.12 nm and an encapsulation efficiency 94.67 ± 0.73%. Optimized niosomal gel (poloxamer 17%) characterized with gelation at 37 °C, pseudoplastic flow and virtuous structural integrity. Both in vitro and ex vivo drug release exhibited sustained release through in situ gel. These findings concluded that lurasidone HCL loaded intranasal niosomal in situ gel embraces significant potential to improve inclusive effectiveness of lurasidone. [ABSTRACT FROM AUTHOR]

The present study investigates the influence of co-administration of different concentrations (2, 6, and 10 mg) of curcumin on goat intestinal permeability of berberine chloride (BBC) using Franz diffusion cell. Data obtained in triplicate from permeability studies were used to calculate percentage cumulative drug release (% CDR), apparent permeability (Papp), flux (J) and enhancement ratio (ER). Co-administration of 6 mg concentration of curcumin with BBC was found to be optimum to enhance the permeability of BBC up to 23.92 ± 0.78 % CDR, over control (8.49 ± 1.45 % CDR). At the optimized concentration of curcumin, permeability characteristics were improved significantly compared to control. The present study reveals the beneficial effect of co-administration of curcumin (6 mg) to promote membrane permeability of BBC which would be expected to improve its bioavailability, thereby therapeutic efficacy. The effect could be attributed to curcumin-mediated inhibition of intestinal efflux pump P-gp, acting as an absorption barrier for BBC. [ABSTRACT FROM AUTHOR]

Three dimensional quantitative structure activity relationship (3D QSAR) investigations were carried out on a series of 5-cyano- N1,6-disubstituted 2-thiouracil derivatives for their locomotor activity. The structures of all compounds were built on a workspace of VlifeMDS3.5 molecular modeling software and 3D QSAR models were generated by applying a partial least square (PLS) linear regression analysis coupled with a stepwise variable selection method. Both derived models were found to be statistically significant in terms of regression and internal and external predictive ability (r² = 0.9414 and 0.8511, q² = 0.8582 and 0.6222, pred_r² = 0.5142 and 0.7917). The QSAR models indicated that both electrostatic and steric interaction energies were contributing significantly to locomotor activity of thiouracil derivatives. [ABSTRACT FROM AUTHOR]

Quantitative structure activity relationship (QSAR) studies of twenty four 5-cyano, N1, 6-disubstituted, 2-thiouracil derivatives were performed for their central nervous system (CNS) depressant (locomotor) activity using VlifeMDS3.5 software. Partial least square (PLS) linear regression analysis coupled with stepwise variable selection method was applied to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The best QSAR model was selected, having correlation coefficient r² = 0.9014 and cross validated squared correlation coefficient q² = 0.8120 with external predictive ability of pred_r² = 0.6692. The QSAR model indicated that the vdWSurfaceArea (van der Waals surface area of the molecule), dipole moment, YcompDipole (y component of the dipole moment) and T_2_F_1 (count of number of double bounded atoms (i.e. any double bonded atom, T_2) separated from fluorine atom by 1 bond in a molecule) were the important determinants for CNS depressant (locomotor) activity. [ABSTRACT FROM AUTHOR]

The effect of polyvinyl pyrrolidone (PVP) K30 and/or l-arginine on etoricoxib-HPβCD complex was investigated. The phase solubility profiles were classified as AL-type, both in absence or presence of auxiliary substances used. The apparent stability constant (Kc) of binary complex obtained at room temperature, 371.80 ± 2.61 M-1, was decreased with the addition of PVP and arginine indicating no benefit of addition of auxiliary substances to promote higher complexation efficiency. Therefore, solid etoricoxib-HPβCD binary systems were prepared and characterized by proton nuclear magnetic resonance spectroscopy (1HNMR), X-ray powder diffractometry, Fourier transformation-infrared spectroscopy, and dissolution studies. Among all binary systems, a lyophilized product showed superior performance in enhancing dissolution of etoricoxib. [ABSTRACT FROM AUTHOR]

The study of inflammatory pain has been one of the most rapidly advancing and expanding areas of pain research in recent years. Studies from our lab have demonstrated the chronic pain-modulating potential of the Phyllanthus species and their probable interaction with various inflammatory mediators involving enzymes like COX-2 and PGE synthase, cytokines like TNF-alpha and IL-1 beta, and with the NMDA receptor. Inflammatory mediators which play a crucial role in chronic inflammatory hyperalgesia and its subsequent modulation were selected for their interactions with 86 structurally diverse phytoconstituents identified from the Phyllanthus species. The docking analysis of the target proteins with the phytochemical ligands was performed using VLifeMDS software. The docking scores and analysis of the interactions of the phytocompounds with target proteins suggest that important molecules like lupeol, phyllanthin, hypopyllanthin, corilagin, epicatechin, and most of the other compounds have the ability to bind to multiple targets involved in inflammatory hyperalgesia. Our study strongly suggests that the findings of the present study could be exploited in the future for designing ligands in order to obtain novel molecules for the treatment and management of chronic pain. [ABSTRACT FROM AUTHOR]

In an attempt to improve the dissolution rate of poorly aqueous soluble diacerein (DCN), solid dispersions (SDs) were prepared with a surfactant Pluronic® F 127 (PXMR) at drug to polymer ratios of 1:0.5, 1:1.5, and 1:2.5 (w/w) by an ordinary melting technique. The interaction of DCN with PXMR in all solid binary systems was evaluated by thin layer chromatography (TLC), Fourier transform infrared spectrometry (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) studies. TLC indicated an absence of chemical interaction of DCN with PXMR whereas FTIR studies demonstrated an existence of strong hydrogen bonding between them. A uniform molecular dispersion of DCN was observed in DSC thermograms, and this finding was further supported by loss of the crystalline and irregular shape of DCN detected in SEM photomicrographs. Dissolution studies were promptly conducted to examine the release rate performance of DCN from all binary systems. The drug dissolution properties of binary systems improved significantly in comparison to crystalline DCN. The rate and extent of DCN release were observed to be strongly dependent on the proportion of PXMR present within the formulations. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopy (1HNMR) studies on inclusion compounds of zaleplon with hydroxypropyl-β-cyclodextrin (HPβCD) were carried out in order to elucidate the strength and binding mode of association. Chemical shift measurements revealed that inclusion complexes of zaleplon and HPβCD were formed by penetration of aromatic rings into the HPβCD cavity from the wider rim side with deep penetration of the amide-substituted ring while inclusion of the cyano-substituted pyrazole ring was shallow. A higher magnitude of ΔδH-3′ and ΔδH-5′ protons of HPβCD indicated higher stability of the lyophilized product than the kneaded one. Even from the values of ΔδH-5′/ΔδH-3′, it could be concluded that zaleplon deeply penetrated inside the HPβCD cavity in the lyophilized product as compared to the kneaded product. The stoichiometry of the inclusion complexes was assessed to be a 1:1 molar ratio with an AL-type of phase solubility curve and a stability constant of 57.89 ± 1.82 M-1, according to Higuchi and Connors. In the case of dissolution experiments, a lyophilized product displayed a higher release rate of zaleplon (DE30: 77.64 ± 5.74) than the kneaded complex and physical mixture. [ABSTRACT FROM AUTHOR]

A simple, sensitive, rapid, accurate and precise spectrophotometric method has been developed for the estimation of diacerein in bulk and pharmaceutical dosage forms. Diacerein shows maximum absorbance at 258.5 nm with molar absorptivity of 4.2258×104l/mol/cm. Beer's law was obeyed in the concentration range of 1-10 μg/ml. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.02 μg/ml and 0.07 μg/ml, respectively. The results of recovery studies (98.68-101.11%) indicated that proposed method is accurate and precise for the determination of diacerein in capsules. [ABSTRACT FROM AUTHOR]