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Background: Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. Methods: In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. Results: Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of −17.23 mV, and in vitro drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, in vitro drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 μm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in in vivo deposition with respect to pure drug deposition, respectively. In vitro drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. Conclusion: PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability. [ABSTRACT FROM AUTHOR]

Crystal engineering provides a unique approach to modulating the physicochemical properties of forming active drug molecules so nowadays pharmaceutical companies and researchers have shown interest in designing and building cocrystals. Creating new crystalline solid structures with altered physicochemical properties such as solubility, bioavailability, tabletability, melting point, stability, and so on. The intermolecular interactions of molecules in the crystal lattice are used to investigate these properties. Numbers of methods for crystallizing the drug are summarised and analyzed, pointing to the advantages and disadvantages that have been highlighted in the literature. This literature review discusses in detail the different types of cocrystals, their mechanisms, methods of cocrystals, applications of cocrystals, and their characterization. The main purpose of this article is to look at what has changed in this field in the last ten years and show what could be learned from better research on cocrystal formation and how it can be used. [ABSTRACT FROM AUTHOR]

The goal of the current study is to design a chronomodulated medicine delivery system for nocturnal acid situations. This strategy is based on a combination of floating and pulsatile principles. With this idea in mind, a floating-pulsatile drug delivery system of lafutidine was created to lengthen the time the dosage form, which has a lag phase followed by a burst release of the drug, stays in the stomach. Accordingly, floating pulsatile tablets were developed in three different steps viz. Preparation of drug-containing core tablets using a super disintegrant, pulsatile layer by compression coating using a mixture of hydrophilic erodible polymers like HPMC E5M and guar gum; and buoyant layer using gel-forming polymer like Carbopol 934P with sodium bicarbonate and citric acid. The effects of the independent variables--the weight ratio of HPMC E5M: Guar gum and the total weight of coating--on the dependent variables, the drug release lag time and cumulative percent drug release at 6 h, were studied using the response surface approach. Developed formulations were evaluated for buoyancy, dissolution, and stability studies. Results indicated the dependence of lag time on the ruptured nature of polymers used. Drug release lag time of optimized batch was found to be 6.20 ± 0.35 h with 98.45 ± 2.24 % of drug release at the end of 8 h. Accelerated stability studies suggested stability of dosage form for at least one month. In order to achieve the best treatment efficacy and increase patient compliance, a successful, stable, floating, pulsatile tablet was created. It can be administered after dinner at around 22:00 h. [ABSTRACT FROM AUTHOR]

The study aimed to develop once a day bilayer tablet of Prazosin HCl (PZH) for the effective treatment of hypertension with a quick-release layer to provide a loading dose while a slow-release layer as a maintenance dose. A statistical approach employing face-centred central composite design and principal component analysis (PCA) to develop bilayer tablets of PZH and scrutinize the critical responses was implemented. Independent factors in the study included the amount of guar gum (X1) and the amount of xanthan gum (X2). Results suggested the significant influence of independent factors on the dependent variables. Optimized formulation showed better performance with the initial first hour period giving a release burst from quick-release layer and then for the next 24 h a sustained release of drug follows. The drug release mechanism was analyzed using various mathematical models of which the optimized formulation exhibited the Higuchi Model. Accelerated stability studies of the preparation suggested no significant difference in the results even after six months. From the study, it could be concluded that a stable, once-a-day bilayer tablet preparation would be feasible in the context of patient compliance. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present investigation was undertaken to develop a psoriatic-like skin inflammation rat model using imiquimod (IMQ) as an inducing agent. MATERIALS AND METHODS: The hairs of the back dorsal portion of the Wistar rats were removed and 80, 100, and 120 mg of IMQ cream (5% w/w) for 10 consecutive days was applied to different groups of rats. Further, psoriasis area severity index was used for calculating the psoriatic score, which included scoring of erythema, scaling, and thickening. Various biochemical parameters, pro-inflammatory cytokines, vascular endothelial growth factor (VEGF), and histopathological examination were also performed. RESULTS: The results demonstrated signs of erythema, scaling, and thickening on group applied with 120 mg and 100 mg of IMQ along with ear thickening. Biochemical evaluation revealed a significant increase in the granulation tissue weight followed by significant decrease in the levels of collagen and hexosamine. The antioxidant parameters superoxide dismutase and catalase were found to decline, while nitric oxide and lipid peroxidation were significantly elevated in skin lesions, also supported by increased pro-inflammatory cytokines expression, i.e., interleukin (IL)-1 β, IL-6, IL-17, tumor necrosis factor-α, and VEGF. Histopathological studies revealed a disturbed natural structure along with increased epidermal proliferation, abnormal differentiation with increased number of keratinocytes in the psoriatic skin tissue. CONCLUSION: From the overall study, we have successfully developed a psoriatic-like skin inflammation rat model for the first time on Wistar strain using IMQ as an inducing agent. [ABSTRACT FROM AUTHOR]

The main objective of the present investigation included a comparative physicochemical, phytochemical along with chromatographic evaluation of Withania somnifera (L.) Dunal roots collected from various Indian climatic zones. The study includes macroscopical, microscopical, physicochemical, phytochemical and chromatographic evaluation of W. somnifera roots collected from different climatic zones (desert, plains, coastal and plateau) of India. Further, chromatographic evaluations were carried out taking Withaferine-A and Withanoloid-A as biomarkers with the help of HPTLC and HPLC analysis. The physicochemical parameters evaluated were found to be within the prescribed limits of the WHO, while the phytochemical analysis showed the higher quantities of phytoconstituents obtained from desert followed by coastal regions. The chromatographic analysis revealed the presence of maximum number of phytoconstituents in sample from coastal and desert region. Further, the quantification of Withaferine-A and Withanoloid-A was carried out using HPTLC and HPLC. The results confirmed higher quantity of both the biomarkers in samples collected from desert followed by coastal region. Thus, the study may be helpful in understanding the role of climatic zones in relation to the variability in phytochemical composition of medicinal plants such as W. somnifera. This will help in selecting the better quality of medicinal plant for preparation of herbal formulations with best therapeutic value that will serve the society. [ABSTRACT FROM AUTHOR]

Background: The plant Eriosema chinense Vogel (Fabaceae) is mainly found in the Eastern Himalayan regions of India and China, and its roots are used traditionally by the tribal people of Meghalaya (India) in treatment of diarrhea. Objective: The objective of the study was to evaluate the potential of roots from E. chinense against enteropathogenic Escherichia coli (EPEC)-induced infectious diarrhea. Materials and Methods: Ethanolic extract of E. chinense (EEC) roots and its chloroform fraction (CEC) were standardized with eriosematin E using high-performance liquid chromatography. The efficacy of EEC (100 and 200 mg/kg, p.o.) and CEC (50 and 100 mg/kg, p.o.) was evaluated against EPEC-induced infectious diarrhea, where behavioral parameters at the 6th and 24th h followed by determination of water content and density of EPEC in stools along with blood parameters examination. Further, the colonic and small intestinal tissues were subjected to biochemical analysis, antioxidant evaluation, determination of ion concentration, Na+/K+-ATPase activity, and histopathology. Results:The results demonstrated a significant antidiarrheal potential of EEC and CEC at both dose levels; however, EEC at 200 and CEC at 100 mg/kg p.o. were found to be more effective, which also reduced EPEC density in stools and also its water content. The treatment also demonstrated a significant restoration of altered antioxidant and electrolyte status and reactivated Na+/K+-ATPase and prevented epithelial tissue damage. Conclusion: The effect may be attributed to an inhibition in intestinal secretion, nitric oxide production, and reactivation of Na+/K+-ATPase. [ABSTRACT FROM AUTHOR]

Bicalutamide (BCT), an anticancer drug, suffers from dissolution rate limited bioavailability and poor micromeritic properties. Spherical crystallization involves the formation of spherical agglomerates with enhanced dissolution properties, obviating the need for further granulation process. The present investigation was focused on spherical agglomeration of BCT by quasi-emulsion solvent diffusion method. All the responses were subjected to principal component analysis to scrutinize the critical attributes. Further for optimization, X1; influence of phase ratio, X2; amount of PEG 6000 and X3; stirring speed on critical dependent variables was studied by employing the Box-Behnken experimental design. The agglomerates exhibited better flow properties, higher bulk density, and improved compressibility compared to pure powder drug. In-vitro release studies revealed enhancement of dissolution properties of poorly soluble BCT. Characterization studies carried out by differential scanning calorimeter and powder X-ray diffractometer revealed crystallinity of drug with decreased intensity in the formulation. Scanning electron microscopy showed spherical shape agglomerates of BCT. The residual solvents were largely below the permitted limits. Spherical agglomerates demonstrated enhanced dissolution properties on account of reduced particle size and partial conversion into amorphous form. Thus, spherical agglomerates of BCT seem to be a promising approach to ameliorate the dissolution properties which might thereby improve its bioavailability. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The objective of the present study was to evaluate wound healing potential of Solanum xanthocarpum extract in streptozotocin‐induced diabetic rats. Methods: Alcoholic extract of the aerial parts (ESX) was subjected to phytochemical estimations and its standardization with chlorogenic acid using HPLC. ESX was then evaluated for wound healing potential in, streptozotocin‐induced diabetic rats using excision and incision wound models on topical and oral treatment Various biochemical evaluations, such as collagen, hexosamine, hyaluronic acid, protein, DNA along with antioxidant parameters, proinflammatory cytokines, VEGF and histopathological examination were also evaluated. Key findings: Extract of S. xanthocarpum depicted the presence of mainly alkaloids, polyphenols, steroids, while content of chlorogenic acid was found to be 8.44% w/w. The maximum effective nature of ESX in healing was observed at 10% gel (topical) and 200 mg/kg (orally) in diabetic rats, where highest healing power was observed when treated both orally and topically. Biochemical evaluations showed significant increase in the levels of collagen, hexosamine, hyaluronic acid, protein, DNA followed by significant decline in the levels of blood glucose, lipid peroxidation, nitric oxide and expression of proinflammatory cytokines, supported by histopathology. Conclusions: The potential healing effect in diabetic rats may be attributed to the presence of chlorogenic acid in combination with other phytoconstituents. [ABSTRACT FROM AUTHOR]

The aim of the present study was to develop a phytochemical profile of Medohar Ark, one of the Ayurvedic formulation used as a potent tool for reducing weight in obese patients and also to perform preclinical evaluation for anti-obesity activity. The physicochemical parameters such as pH, viscosity, specific gravity and total solid content of Medohar Ark marketed (MAM), Medohar Ark in-house (MAIH) and distilled cow urine (DCU) were performed along with phytochemical screening and chromatographic (HPTLC and HPLC) study using Crocin as a biomarker. Phytochemical screening revealed the presence of alkaloids, flavonoids, tannins, sterol, carbohydrates and saponins in MAIH and MAM. The HPTLC analysis revealed that, MAIH contained 4.58 % w/w of Crocin, whereas in MAM, Crocin was not detected. However, HPLC analysis of MAIH and MAM showed that MAIH and MAM contained 4.56 % w/w and 1.23 % w/w of crocin, respectively. The pharmacological evaluation concluded that, MAIH showed better result as compared to MAM in reduction of body weight of rats in high fat diet (HFD) rat model. From the lipid profile and antioxidant evaluations of animals, it was observed that there was a significant restoration in altered lipid profile and antioxidant status of HFD induced rats treated with MAM and MAIH, which was also confirmed through histopathological studies showing very less fat deposition. The overall study concludes that the Medohar Ark has a significant anti-obesity activity especially in case of in-house formulation, which can be used as a major tool for obesity management in human healthcare. [ABSTRACT FROM AUTHOR]

The work is based on pulsatile principles to deliver a programmed dose of Irbesartan, an angiotensin-II receptor antagonist for chronotherapy of hypertension induced by excessive secretion of aldosterone, thereby lower the blood pressure at early morning. Solid dispersion of Irbesartan, a BCS class II drug, was prepared by using Poloxamer-188 by melt method in ratio of 1:1 to increase the dissolution properties of drug. Compressed coated pulsatile tablets included a core layer consisting of Kyron T-134 as a super-disintegrant and pulsatile layer comprising of HPMC K4M and Eudragit RLPO. The prepared core tablets were evaluated for weight variation, hardness, thickness, friability, drug content, disintegration time and In vitro dissolution studies. Final core tablet (C8) was selected on the basis of disintegration time (23.33 ± 2.08 s). For optimization Face centred central composite design was employed to study the effect of independent variables viz. Weight ratio of HPMC K4M: Eudragit RLPO (X 1 ) and Total weight of coating (X 2 ) on dependent variables viz. Drug release lag time (Y 1 ) and Drug release after lag time within 15 min (D 15 ) (Y 2 ). Results revealed positive influence of independent factors on responses. The data were statistically analyzed using ANOVA and were found to be statistically significant (P < .05). Mathematical modeling for kinetic studies revealed that the release profile after lag time followed first order kinetics. Accelerated stability studies for one month at 40 ± 2 °C/75 ± 5% RH showed no remarkable changes concluding that a successful pulsatile drug delivery system of Irbesartan was developed. [ABSTRACT FROM AUTHOR]

The aim of the present study was to perform a comparative phytochemical and pharmacological evaluation of organically and non-organically cultivated nutritional Centella asiatica collected at different time intervals of harvesting. The fertilizers and pesticides applied in case of organic cultivation included combination of medicinal plants along with other natural products and the harvesting was carried out after 1st, 2nd and 3rd month of cultivation. From all the physicochemical parameters evaluated, the leaves collected after third month of harvesting showed higher ash values suggesting higher contents of sand or earthy matter along with higher moister content. The results from the phytochemical evaluations revealed that, the samples collected from first harvesting showed higher quantities of phytoconstituents. This was also confirmed through chromatographic studies using HPTLC showing higher content of Asiatic acid in samples collected after first month of harvesting, which was more pronounced in case of organic cultivation. The pharmacological evaluation included comparative nootropic activity of different samples of organic and nonorganic C. asiatica . The results depicted a significant (p < 0.05) reduction in escape latency of mice treated with 100 mg/kg, p.o. of organic and nonorganic cultivated C. asiatica collected after first month of harvesting and also showed a significant increase in the spatial working memory, which included acquisition and retrieval trials. Further, the two samples also revealed significant inhibition in AChE activity as observed in different brain region i.e. hippocampus, prefrontal cortex and amygdale, where organically cultivated C. asiatica was found to be more effective. Thus, from the overall observation, it may be concluded that, the organically cultivated C. asiatica , if collected after first month of cultivation shows the best memory enhancing activity as compared to other time interval of harvesting. [ABSTRACT FROM AUTHOR]

The aim of present investigation is to improve dissolution rate of poor soluble drug Zotepine by a self-microemulsifying drug delivery system (SMEDDS). Ternary phase diagram with oil (Oleic acid), surfactant (Tween 80) and co-surfactant (PEG 400) at apex were used to identify the efficient self-microemulsifying region. Box–Behnken design was implemented to study the influence of independent variables. Principal Component Analysis was used for scrutinising critical variables. The liquid SMEDDS were characterised for macroscopic evaluation, % Transmission, emulsification time andin vitrodrug release studies. Optimised formulation OL1 was converted in to S-SMEDDS by using Aerosil®200 as an adsorbent in the ratio of 3:1. The S-SMEDDS was characterised by SEM, DSC, globule size (152.1 nm), zeta-potential (−28.1 mV), % transmission study (98.75%),in vitrorelease (86.57%) at 30 min. The optimised solid SMEDDS formulation showed faster drug release properties as compared to conventional tablet of Zotepine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The plant Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) is one of the members of the dashamula (ten roots) in Ayurvedic system of medicine. The stem and fruits are used as an antipyretic, antiasthmatic and is prescribed in skin infections and for relief in burning sensation in the feet accompanied by vesicular eruptions. Objective To scientifically validate the anti-psoriatic potential of Solanum xanthocarpum stem in Imiquimod-induced psoriatic mice model. Materials and methods Ethanolic stems extract of Solanum xanthocarpum (ESX) was first subjected to phytochemical screening and quantification of identified phytoconstituents, which was further standardized with the help of HPTLC using chlorogenic acid as a marker. The extract was then subjected to acute oral toxicity and skin irritability study for determining the safety profile of the extract. Imiquimod-induced psoriatic mouse model was then performed to check the efficacy of extract against psoriasis, where treatment was carried out for 15 days both topically (Gel at 2.5%, 5% and 10%) as well as orally (at 100, 200 and 400 mg/kg p.o.) and their Psoriasis Area Severity Index (PASI) was calculated. The study also included determination of levels of TNF-α, IL-1β, IL-6 and IL-17 in the animal tissues, which further included biochemical evaluations such as total collagen, hexosamine, hyaluronic acid DNA, protein antioxidant profiles such as lipid peroxidation, nitric oxide, superoxide dismutase and catalase along with histopathological studies of the tissues. Result ESX showed the presence of mainly phenols, tannins, flavonoids, alkaloids and carbohydrates, while chlorogenic acid was reported to be 3.49% w/w. The Imiquimod-induced psoriatic mouse model, depicted a potent anti-psoriatic activity of the extract both topical (10%) and oral (200 and 400 mg/kg p.o., as evident through PASI grading The effect was found to be more prominent in case of topically treated as compared to orally treated mice. The results also showed a significant inhibition in the expression of TNF-α, IL-1β, IL-6 and IL-17 in treated animal tissues and also showed significant restoration of the altered biochemical parameters along with reduced hyperkeratinisation as observed through histopathology. Conclusion The study scientifically justified the anti-psoriatic activity of the ESX, which may be attributed to inhibition in the expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-17. Further, the observed antioxidant, antimicrobial and cellular proliferative activities may act as a contributing factor in treatment of psoriasis, which may be attributed to the presence of chlorogenic acid along with other phytochemicals in combination. [ABSTRACT FROM AUTHOR]

Background: Roots of the plant Eriosema chinense Vogel (Fabaceae) is distributed mainly over the Eastern Himalayan region of India and China. The roots of the plant are used as a vegetable by the people of Northern Australia, China and North East India and are used traditionally by the tribal people of Meghalaya (India) for the treatment of diarrhoea. It has been reported to have significant antidiarrhoeal, cytotoxic and antimycobacterial activity.Purpose/objective: The present investigation was undertaken to isolate a lead molecule responsible for the observed antidiarrhoeal activity.Methods: Eriosematin E, a prenylated flavanone, was isolated using column chromatography and was characterized by comparing its melting point and spectroscopic data (UV, IR, 1H NMR, 13C NMR, Mass Spectra) from literature. Eriosematin E (2.5, 5 and 10mg/kg p.o.) was then screened for normal faecal excretion rate and castor oil-induced diarrhoea models in rats. Further, it was examined for small intestinal transit, intestinal fluid accumulation and PGE2 induced enteropooling models in rats. Biochemical estimations and Na+ and K+ concentration in intestinal fluid were also determined along with colonic histopathological studies.Results: The results illustrated a significant (P< 0.05) reduction in normal faecal output at 10mg/kg p.o. after 5th and 7thh of treatment and also showed maximum protection of 69.43% from diarrhoea in the castor oil-induced diarrhoea model. Significant results were also observed at the maximum effective dose of eriosematin E (10mg/kg p.o.) in inhibiting peristaltic index (small intestinal transit) and reducing intestinal fluid volume of castor oil induced and PGE2 induced enteropooling models. Further, eriosematin E restored all the alterations in biochemical parameters such as nitric oxide, protein, DNA, superoxide dismutase, catalase and lipid peroxidation. It also significantly recovered Na+ and K+ loss from body and confirmed its protective nature through the histopathological studies.Conclusion: The study corroborates the antidiarrhoeal potential of eriosematin E which may be attributed to its antisecretory and antioxidant potential. [ABSTRACT FROM AUTHOR]

Background: Delhi, the capital of India, has suffered many outbreaks of dengue in recent past and despite the obvious magnitude of problem, very scarce evidence exists that documents the knowledge, awareness and practices of the people regarding dengue. Aim: To assess the knowledge and practices related to control of dengue fever and to assess the differences in knowledge and practices based on sex and literacy. Materials and Methods: A cross-sectional study was conducted among persons visiting a tertiary care hospital in New Delhi. A systematic sampling procedure was adopted and a pretested questionnaire was used. Results: A total of 215 individuals were interviewed. Majority of the respondents (96.3%) had heard about dengue. The important sources of information were television (54.9%) and newspaper/ magazines (51.7%). Around 89% of the study participants considered dengue as "serious problem." Nearly 86% participants were aware of the spread of dengue by mosquitoes while 73% were aware of one of the correct breeding sites of Aedes mosquito. Mosquito mats/ liquidators were used by 61% of respondents, coils by 56% and repellant creams by 22%. Conclusion: The awareness regarding dengue and mosquito control measures was satisfactory to an extent. Programs should focus that this knowledge gets translated into practice. [ABSTRACT FROM AUTHOR]

The plant Solarium xanthocarpum, Schrad. & Wendl. (Solanaceae) is one of the members of the dashamula (ten roots) in Ayurvedic system of medicine. The stem and fruits are used as an antipyretic, antiasthmatic and is prescribed in skin infections. The aim of the present investigation is to scientifically validate the anti-psoriatic potential of S. xanthocarpum stem. Ethanolic stems extract of S. xanthocarpum (ESX) was first subjected to phytochemical screening and quantification of identified phytoconstituents, which was further standardized with the help of HPTLC using chlorogenic acid as a marker. The extract was then subjected to acute oral toxicity study for determining the safety profile of the extract. Imiquimod-induced psoriatic mouse model was used for the study where treatment was carried out for 15 days both topically (Gel at 2.5, 5 and 10%) as well as orally (at 100, 200 and 400 mg/kg p.o.) and their Psoriasis Area Severity Index (PASI) was calculated. The study also includes determination of levels of of TNF-α, IL-1β, IL-6 and IL-17 in the animal tissues which further included biochemical evaluations such as total collagen, hexosamine, hyaluronic acid DNA, protein antioxidant profiles such as lipid peroxidation, nitric oxide, superoxide dismutase and catalase along with histopathological studies of the tissues. ESX showed the presence of mainly phenols, tannins, flavonoids, alkaloids and carbohydrates, while the chlorogenic acid was reported as 3.49% w/w. The imiquimod-induced psoriatic mouse model, depicted a potent antipsoriatic activity of the extract both topical (10%) and oral (200 and 400 mg/kg p.o., as evident through PASI grading The effect was found to be more prominent in case of topically treated as compared to orally treated mice. The results also showed a significant decrease in the levels of TNF-α, IL-1β, IL-6 and IL-17 in treated animal tissues, and also significant restoration of the altered biochemical parameters. Also, the histopathological studies revealed the regeneration of the fibroblast and sweat glands. The study scientifically justified the anti psoriatic activity of the ESX, which may be attributed to the cumulative effect of the phytoconstituents identified in the extract such as chlorogenic acid which has already been reported to have significant role in skin infections. [ABSTRACT FROM AUTHOR]

Zotepine is an atypical antipsychotic drug used in the treatment of schizophrenia. However, its poor dissolution properties limit its therapeutic efficacy. In this investigation, a series of nanosuspension-containing zotepine were prepared employing media milling method with an aim to improve its dissolution properties and oral bioavailability. Briefly, Box-Behnken design was applied to investigate the influence of various independent variables such as X 1 - amount of stabilizer, X 2 - amount of milling agent, and X 3 - milling time on the performance of the formulation. Dissolution studies revealed enhancement of dissolution rate as compared to pure drug. Solid state characterization (DSC, PXRD, and SEM) studies demonstrated no polymorphic changes in drug after lyophilization of media-milled nanosuspension. In vivo pharmacokinetic studies of lyophilized nanosuspension was carried out in rat and the results exhibited significant improvement in C max and AUC 0-t , about 450.0 and 287.45%, respectively, suggesting amelioration in oral bioavailability by 2.87-fold higher as compared to pure drug. Accelerated stability studies of the optimized lyophilized formulation at 40°C and 75% RH suggested stability of the nanocrystals for at least a 6-month period. The obtained nanocrystals successfully showed dissolution enhancement and improved oral bioavailability of poorly water-soluble drug, zotepine., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Purpose: Present investigation was aimed to fabricate nanocrystal of exemestane, an anticancer drug with poor dissolution properties and oral bioavailability., Methods: Influence of various process parameters on the formulation of exemestane nanosuspension using media milling technique were investigated in the trial batches. Box-Behnken design was applied with independent variables identified in the preliminary studies, viz. X1 -Milling time, X2 -Amount of stabilizer and X3 -Amount of milling agent. In vitro dissolution and in vivo studies were carried out. Solid state characterization (PXRD, SEM, and DSC) studies demonstrated physical changes in drug due to nano-crystallization. Accelerated stability studies of optimized formulation were carried out., Results: Individual process attributes exhibited a significant effect on the average particle size of exemestane nanosuspension. Dissolution studies revealed enhancement in drug release rate as compared to pure exemestane powder. The in vivo pharmacokinetic parameters of exemestane nanosuspension showed significant improvement in Cmax and AUC0-t, about 283.85% and 271.63%, respectively suggesting amelioration in oral bioavailability by 2.7-fold as compared to pure exemestane. Accelerated stability studies of the optimized formulation suggested stability of the nanocrystals for at least a six-month period., Conclusion: Nanocrystals prepared by media milling technique were successful in improving the poor dissolution properties and oral bioavailability of exemestane., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The main objective of the present study was to evaluate the potential of eriosematin E (ECM) isolated from the roots of Eriosema chinense against enteropathogenic Escherichia coli (EPEC) induced diarrhoea. ECM isolated from the bioactive chloroform fraction of E. chinense was subjected to antidiarrhoeal evaluation on rats against diarrhoea, induced by the oral suspension of EPEC. The study included evaluation of behavioral parameters for 6 h and up to 24 h of induction, followed by estimation of water content, the density of EPEC in stools and evaluation of various blood parameters. Further, the colonic and small intestinal tissues were subjected to biochemical estimations, antioxidant evaluation, determination of ion concentration, Na + /K + -ATPase activity, pro-inflammatory cytokines assessment and histopathology. Finally, the impact of ECM on Na + /K + -ATPase was studied through molecular docking studies. Significant antidiarrhoeal potential of ECM was demonstrated at 5 and 10 mg/kg, p.o., however, ECM at 10 mg/kg, p.o. was found to be more effective, as confirmed through higher % protection, density of EPEC in stools and water content of stools. ECM also significantly increased the level of WBC, Hb, platelets and revealed restoration of altered antioxidants, pro-inflammatory cytokines (IL-1β and TNF-α) status and also reactivated the suppressed Na + /K + -ATPase activity, which was also confirmed through docking studies showing H-bonding of hydroxyl group of ECM with amino acids Asp 190, Asn 167 and Glu 169 thus, maintaining proper electrolyte balance and also prevented epithelial tissue damage. The overall effect of ECM may be attributed to the decline in the elevated level of cytokines, inhibition in nitric oxide production and reactivation of Na + /K + -ATPase activity resulting in reduced intestinal secretion., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of the present work was to improve the dissolution characteristics of the poorly water soluble antiepileptic drug lamotrigine (LMN) by inclusion complexation using hydroxy propyl beta-cyclodextrin (HP beta-CD) by co-evaporation technique and by, solid dispersion, prepared by the melt method using poloxamer 407 (L 127). Phase solubility studies showed AL type curves with both the carriers. Dissolution of LMN was significantly improved (p < 0.05) by inclusion complexation and solid dispersion preparation. Results of solid state characterization performed by Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry and Powder X-ray Diffractrometry techniques revealed a decrease in the crystallinity of LMN that might be accounting for improvement in the dissolution properties as seen from dissolution studies.