Phenylboronic acid modified lipid nanocarriers mediated co-delivery of immunocytokine TRAIL and gamma-secretase inhibitor to triple negative breast cancer cells and cancer stem cells.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with high rates of tumor relapse and metastasis. The existing drugs for treatment of TNBC are unable to target the cells of origin (breast cancer stem cells) of TNBC. TNF-α related apoptosis inducing ligand (TRAIL) has propensity to target TNBC cells including cancer stem cells. However, resistance to TRAIL due to activation of anti-apoptotic mechanisms is a limitation for TRAIL based anticancer therapy for TNBC. In the present study we propose an hypothesis for effective targeting of triple negative breast cancer by overcoming TRAIL resistance.

Profiling and determination of phenolic compounds in poly herbal formulations and their comparative evaluation.

Nowadays, plants have been considered as powerful agents for treatment of disorders regarding to their traditional use. Plants have a special role in the treatment of various diseases in Ayurveda (Indian Traditional Medicine). Diabetes with their devastating outcomes has been discussed in Ayurveda as well. In the present study, a marketed polyherbal products (DBC & DMV), retrieved from Ayurveda, was purchased from market and its pharmacognostic standardization were performed. Quality control test for the Ayurveda tablets were performed as per Indian Pharmacopoeia. In addition to the dissolution studies for the poly herbal Ayurveda marketed formulations were assessed based on the phenolic content. Fingerprinting of phytochemical constituents of DBC & DMV was performed using spectroscopical (like IR and UV) and chromatographic techniques like HPTLC and TLC. The results showed that DBC & DMV was successfully passed quality control tests. Moreover, DBC & DMV exhibited different pharmacognostic behavior of all herbs present in the product. In addition, TLC, IR and HPTLC fingerprinting of DBC & DMV demonstrated the presence of several phenolic constituents corresponding to the poly herbs. Regarding to the role of phenolic compounds in diabetic process, DBC & DMV could be an appropriate candidate for diabetic with respect to its traditional use in Ayurveda formulation. Moreover, HPTLC fingerprinting could be utilized as an applicable method for quality control of the prepared formulation.

Self-emulsifying drug delivery system for enhanced solubility of asenapine maleate: design, characterization, in vitro, ex vivo and in vivo appraisal.

Self-emulsifying drug delivery systems (SES) were developed to improve oral bioavailability of asenapine maleate (ASM), an antipsychotic drug with challenging amphiphobic nature and extensive pre-systemic metabolism. ASM-SES was prepared by choosing the proportion of oil, surfactant, co-surfactant from constructed phase diagram. The in vitro and ex vivo evaluation was done. In vivo evaluation was done through pharmacokinetic and pharmacodynamic studies. Role of lymphatic absorption was studied by lymphatic absorption inhibition study. A formulation consisting of 9.9%, 59.4%, 29.7% and 1% of oil, surfactant, co-surfactant, and drug respectively was considered as optimized formulation. After various evaluation test, the globule size and zeta potential for optimized formulation (SES4) were found to be 137.9 nm and -28.8 mV respectively. A maximum of 99.64 ± 0.16% of ASM was released from SES4 in 60 minutes of time. The flux (ex vivo study) increased by 2.33 folds, which prove the enhanced release and permeation of ASM when loaded into SES. The animals administered with SES4 showed higher activity and good pharmacodynamic response than the control and ASM-Suspension, which may be due to the greater availability of the drug. The maximum pharmacodynamic response was observed at the tmax determined by Pharmacokinetic studies. The bioavailability increased by 1.64 folds with 16.55 ± 3.11% as extend of lymphatic absorption (r = 0.9732). Good in vitro in vivo correlation was observed. ASM-SES is a novel approach to effectively deliver ASM and improve the oral bioavailability.

Profiling and determination of phenolic compounds in Indian marketed hepatoprotective polyherbal formulations and their comparative evaluation.

BACKGROUND: Nowadays, plants have been considered as powerful agents for treatment of disorders due to their traditional use. Plants have a special role in the treatment of various diseases in Ayurveda. Liver disorders with their devastating outcomes have been discussed in Ayurveda as well. OBJECTIVES: In the present study, polyherbal products (L52 and L38) were retrieved from Ayurveda and its pharmacognostic standardization was performed. MATERIALS AND METHODS: Quality control test for the Ayurveda tablets were performed as per Indian Pharmacopoeia. Dissolution studies of polyherbal Ayurveda marketed formulations were assessed based on the phenolic content. Fingerprinting of phytochemical constituents of L52 and L38 was performed using spectroscopical (like IR and UV) and chromatographic techniques like HPLC, HPTLC and TLC. RESULTS: The results showed that L52 and L38 successfully passed quality control tests. Moreover, L52 and L38 exhibited different pharmacognostic behavior of all herbs present in the product. In addition, TLC, IR, HPTLC and HPLC fingerprinting of L52 and L38 demonstrated the presence of several phenolic constituents corresponding to the polyherbs. CONCLUSION: Regarding the role of phenolic compounds in the treatment of hepatitis, L52 and L38 could be appropriate candidates for hepatitis with respect to their traditional use in Ayurveda formulation. Moreover, HPTLC and HPLC fingerprinting could be utilized as an applicable method for quality control of the prepared formulation.

Determination of antioxidant capacity, α-amylase and lipase inhibitory activity of Crotalaria juncea Linn in vitro inhibitory activity of Crotalaria Juncea Linn.

The present study involves the determination of antioxidant capacity and in vitro α-amylase and lipase inhibitory activity of the Crotalaria juncea Linn extract. The content of polyphenols, flavonoids, and tannins in the extracts was estimated by spectrophotometry. Antioxidant activity on goat liver lipid peroxidation and linoleic acid emulsion were determined and α-amylase and lipase inhibitory activity was also evaluated. All the extracts had shown antioxidant property, α-amylase, and lipase inhibitory properties. Aqueous extract was found to show maximum antioxidant activity on goat liver. Antilipid peroxidation and antioxidant activity were determined to be 66.94 ± 0.616 (p < .01) and 59.54 ± 0.2 (p < .01), respectively. Maximum α-amylase and lipase inhibitory activities of 71.42 ± 1.37 (p < .01) and 57.14 ± 2.74% (p < .01), respectively, were exhibited by macerated methanol extract. The results had shown that all the extracts exhibited low inhibition and antioxidant activity as compared to standard.

A novel validated UPLC method for quantitation of lopinavir and ritonavir in bulk drug and pharmaceutical formulation with its impurities

A simple gradient Ultra Performance liquid chromatographic method (UPLC) was developed for determination of lopinavir and ritonavir from its related impurities and assay for the first time. This method involves the use of a C18 (Acquity UPLC BEH C18, 50 × 2.1 mm, 1.7 µm) column thermostated at 30 oC using triethylamine (pH 2.2): 0.1% H3PO4 in acetonitrile and methanol (85:15) as mobile phase in gradient elution mode. A Photo Diode Array (PDA) detector set at 215 nm was used for detection with flow rate 0.4 mL/min. This method was validated over the range of limit of quantitation (LOQ) to 50 to 150% of impurity specification limit and of working concentration for assay. The developed method was validated for linearity, range, precision, accuracy and specificity. This method was successfully applied for content determination of lopinavir and ritonavir in pharmaceutical formulations. This method can be conveniently used in quality control laboratory for routine analysis for assay and related substances as well as for evaluation of stability samples of bulk drugs and pharmaceutical formulations.

Desenvolveu-se, pela primeira vez, método de cromatografia líquida de ultra-eficiência (UPLC), com gradiente simples, para a determinação de lopinavir e ritonavir e suas impurezas relativas. Esse método envolve o uso de C18 (Acquity UPLC BEH C18, 50 × 2,1 mm, 1,7 µm), termostatizada a 30 oC, utilizando-se trietilamina (pH 2,2) e fase móvel de H3PO4 0,1% em acetonitrila e metanol (85:15), em eluição por gradiente. Detector de arranjo de fotodiiodo (PDA), fixado a 215 nm, foi utilizado para a detecção, com fluxo de 0,4 mL/min. Esse método foi validado em faixa de limite de quantificação (LOQ) de 50 a 150% de limite de impureza e da concentração de trabalho para o ensaio. O método desenvolvido foi validado quanto à linearidade, faixa, precisão, exatidão e especificidade. Esse método foi aplicado com sucesso para a determinação de lopinavir e de ritonavir em formulações farmacêuticas. Tal método pode ser convenientemente utilizado em laboratório de controle de qualidade, não só para análise de rotina e ensaio de substâncias relacionadas, como também para a avaliação da estabilidade de amostras a granel ou em formulações farmacêuticas.

Molecular docking studies of withanolides against Cox-2 enzyme.

Withaniasomnifera (Ashwaganda) belonging to the family solanaceae is the subject of our present study. Withanoloides which are the major chemical constituents have been proved of interest because of their structural variations in the hybrids of different races. Docking is the process which brings the two structures together. In the present study we focus the extensive use of tool and graphical software for the identification of the binding energy of selected Withanolides like Withaferin -A, Withanolide-D from Withaniasomnifera and to screen the phytoconstituents that will dock/bind to the active sites of COX-2 enzyme. The relief from the symptoms of inflammation and pain can be by the Pharmacological inhibition of COX which involves the prediction of potential ligand for the treatment of inflammation. The energy value of docking between the target and the phytoconstituents under investigation and comparison with Diclofenac sodium was taken into consideration for coming into conclusion regarding the best pose and the binding ability.

Formulation and evaluation of bi-layer floating tablets of ziprasidone HCl and trihexyphenidyl HCl / Formulação e avaliação de bi-camada comprimidos flutuantes de ziprasidona HCl e HCl triexifenidila

The purpose of this research study was to establish ziprasidone HCl NR 40 mg and trihexyphenidyl HCl SR 4mg in the form of bi-layer sustained release floating tablets. The tablets were prepared using sodium HPMC K4M / HPMC K15M as bio-adhesive polymers and sodium bicarbonate acting as a floating layer. Tablets were evaluated based on different parameters such as thickness, hardness, friability, weight variation, in vitro dissolution studies, content of active ingredient and IR studies. The physico-chemical properties of the finished product complied with the specifications. In vitro release from the formulation was studied as per the USP XXIII dissolution procedure. The formulations gave a normal release effect followed by sustained release for 12 h which indicates bimodal release of ziprasidone HCl from the matrix tablets. The data obtained was fitted to Peppas models. Analysis of n values of the Korsmeyer equation indicated that the drug release involved non-diffusional mechanisms. By the present study, it can be concluded that bi-layer tablets of ziprasidone HCl and trihexyphenidyl HCl will be a useful strategy for extending the metabolism and improving the bioavailability of Ziprasidone HCl and Trihexyphenidyl HCl.

O propósito deste trabalho foi preparar ziprasidona. HCl NR 40 mg e triexifenidila.HCl SR 4 mg na forma de comprimidos efervescentes bicamada de liberação controlada. Os comprimidos foram preparados utilizando HPMC K4M / HPMC K15M sódico como polímero bioadesivo e bicarbonato como camada efervescente. Os comprimidos foram avaliados quanto a diferentes parâmetros, como espessura, dureza, friabilidade, variação de peso, dissolução in vitro, conteúdo do ingrediente ativo e estudos de IV. As propriedades físico-químicas dos produtos finais cumprem as especificações. A liberação in vitro da formulação foi estudada de acordo com o procedimento de dissolução da USP XXIII. As formulações resultaram em liberação normal, seguida por liberação controlada por 12 h, o que indica a liberação bimodal de cloridrato de ziprasidona dos comprimidos matriz. Os dados obtidos se adequaram aos modelos de Peppas. A análise de valores de n da equação de Korsmeyer indicou que a liberação do fármaco envolveu mecanismos não difusionais. Por este estudo, pode-se concluir que os comprimidos bicamada de ziprasidona.HCl e de triexifenidila.HCl serão um bom caminho para estender o metabolismo e para melhorar a biodisponibilidade de ziprasidona.HCl e de triexifenidila.HCl.

Anti lipid peroxidation activity of Piper trioicum Roxb. and Physalis minima L. extracts.

Attempt has been made to evaluate free radical scavenging activity of ethanolic extract of Piper trioicum Roxb. and Physalis minima L. individually. In this study goat liver has been used as lipid source. This in vitro evaluation was done by measuring the malondialdehyde (MDA) of tissue homogenates. The results suggest that the ethanolic extract of the Piper trioicum Roxb. and Physalis minima L. has the ability to suppress the lipid peroxidation and it was also found that Piper trioicum Roxb. extract has more activity than Physalis minima L. extract.