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Exploring the potential of porous silicas as a carrier system for dissolution rate enhancement of artemether

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Asian Journal of Pharmaceutical Sciences 2016年第6期11卷 760-770页

作者： Jaywant N.Pawar Harita R.desai Kailas K.Moravkar deepak K.Khanna purnima d.amin department of Pharmaceutical Sciences and Technology Institute of Chemical Technology(Elite Status)N.P.MargMatunga(E)Mumbai 400019India Applied Technology Inorganic MaterialsEvonik Degussa India Pvt.Ltd.Krislon HouseSakivihar RoadSakinakaAndheri(East)Mumbai 400069India

Malaria is a parasitic and vector determined blood-conceived infectious disease transmitted through infected mosquitoes. Anti-malarial drug resistance is a major health problem, which hinders the control of malaria. A Results of a survey of drug-resistant malaria demonstrated safe proclivity to nearby all anti-malarial regimes accessible except from artemisinin and its derivatives. Artemether is a BCS class IV drug effective against acute and severe falciparum malaria;hence there is a strong need to improve its solubility. Silica is one of the most widely studied excipients. Silica can be used in solubility enhancement by preparing its solid solution/dispersion with the drug. The objective of this research was to improve dissolution rate of Artemether using non-precipitated porous silica(Aeroperl 300 Pharma) and precipitated silica like EXP. 9555, EXP. 9560, and EXP. 9565. Specific surface area calculated from BET method of porous silicas viz. APL 300(A), Exp. 9555(B), Exp. 9560(C), Exp. 9565(d) was found to be 294.13 m^2/g(A), 256.02 m^2/g(B), 213.62 m^2/g(C) and 207.22 m^2/g(d) *** drug release from the developed formulation was found to be significantly higher as compared to neat ARM. This improved solubility and release kinetics of ARM may be attributed to high surface area, improved wettability and decreased crystallinity. Solid-state characterization of the developed optimized formulation F3 was carried out with respect to FTIR chemical imaging, XRd,SEM, and dSC. All the porous silicas which we have explored in the present context showed a significant capability as a carrier for solubility enhancement of ARM.

关键词： Artemether Solubility Solid dispersion Porous silica Aeropearl 300

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development of amorphous dispersions of artemether with hydrophilic polymers via spray drying: Physicochemical and in silico studies

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Asian Journal of Pharmaceutical Sciences 2016年第3期11卷 385-395页

作者： Jaywant N.Pawar Rahul T.Shete Avinash B.Gangurde Kailas K.Moravkar Sharadchandra d.Javeer divakar R.Jaiswar purnima d.amin department of Pharmaceutical Sciences and Technology Institute of Chemical Technology Nathalal Parekh Marg

Artemether(ARM) is a poorly water soluble and poorly permeable drug effective against acute and severe falciparum malaria, hence there is a strong need to improve its solubility. The objective of the study was to enhance the solubility and dissolution rate of ARM by preparation of solid dispersions using spray-drying technique. Solid dispersions of ARM were prepared with Soluplus, Kollidon VA 64, HPMC and Eudragit EPO at weight ratios of 1:1, 1:2,1:3 using spray drying technology, and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry(dSC), and X-ray powder diffraction(XRd) to identify the physicochemical interaction between drug and carrier, as well as effect on *** prepared solid dispersion of ARM with polymers showed reduced crystallinity as compared to neat ARM, which was confirmed by dSC and XRd. drug/polymer interactions were studied in-silico by docking and molecular dynamics which indicated formation of van der Waals type of interactions of ARM with the polymers. Based on solubility studies, the optimum drug/Soluplus ratio was found to be 1:3. The dissolution studies of formulation Sd3 showed highest drug release up to 82% compared to neat ARM giving only 20% at 60 minutes. The spray-dried products were free of crystalline ARM; possessed higher dissolution rates, and were stable over a period according to ICH guidelines. These findings suggest that an amorphous solid dispersion of ARM could be a viable option for enhancing the dissolution rate of ARM.

关键词： Artemether Spray drying Solid dispersion In silico study docking ARM artemether Sds solid dispersions

Continuous melt granulation to develop high drug loaded sustained release tablet of Metformin HCl

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Asian Journal of Pharmaceutical Sciences 2017年第1期12卷 37-50页

作者： Pradnya Vaingankar purnima amin department of Pharmaceutical Sciences and Technology Institute of Chemical Technology University under Section 3 of UGC Act–1956 Elite Status and Centre of Excellence–Government of Maharashtra

The present work explores the application of melt granulation technology to develop a high drug loaded sustained release matrix tablet of Metformin HCl using hydroxypropylcellulose(HPC) as a hydrophilic binder and stearic acid as an extrusion aid for producing cohesive granules. This novel approach allowed the use of a minimum number of excipients to reduce the tablet size, and to enhance compressibility of the drug. This also offered a cost effective method owing to the elimination of a ‘drying step’ prevalent in wet granulation ***, this research also focuses on resolving the processability issues associated with the use of HPC Nisso-H at high drug loading. The thermal lubricants were screened for this purpose and evaluated for their impact on extrudability, granule and tablet characteristics. Stearic acid was selected as the thermal lubricant, which not only contributed to the inhibition of burst release, but also improved the flow property of the *** developed matrix tablet(75% drug loading) resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRd and dSC analysis revealed the crystalline state of the ***, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose,highly water soluble drug otherwise difficult to process using standard batch-granulation.

关键词： Metformin hydrochloride Hydroxypropylcellulose High drug loaded tablet Melt granulation

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development and evaluation of lafutidine solid dispersion via hot melt extrusion:Investigating drug-polymer miscibility with advanced characterisation

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Asian Journal of Pharmaceutical Sciences 2014年第2期9卷 92-106页

作者： Ritesh Fule purnima amin department of Pharmaceutical Sciences and Technology Institute of Chemical TechnologyNathalal Parekh MargMatungaMumbai 400019MaharashtraIndia

In current study,immediate release solid dispersion(Sd)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)*** Soluplusused as a primary solubilizing agent,with different concentrations of selected surfactants like PEG 400,Lutrol F127(LF127),Lutrol F68(LF68)were used to investigate their influence on formulations processing via *** amorphous glassy solid dispersion was found to be thermodynamically and physicochemically *** the contrary,traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry(dSC),X-ray diffraction(XRd),scanning electron microscopy(SEM)and Raman *** micro spectrometry had the lowest detection limit of LAFT crystals compared with XRd and *** Force microscopy(AFM)studies revealed drugpolymer molecular miscibility and surface interaction at micro level.1HeCOSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus,with chemical shift drifting and line *** simulation studies using computational modelling showed intermolecular interaction between *** rate and solubility of LAFT was enhanced remarkably in developed Sd *** ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT *** obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.

关键词： Lafutidine Solid dispersion Hot melt extrusion dissolution rate Raman spectroscopy Atomic force microscopy

Microencapsulation by Spray drying of Vitamin A Palmitate from Oil to Powder and Its Application in Topical delivery System

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Journal of Encapsulation and Adsorption Sciences 2017年第1期7卷 10-39页

作者： Avinash B. Gangurde purnima d. amin department of Pharmaceutical Sciences and Technology Institute of Chemical Technology Mumbai India

Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degradation especially in an aqueous environment. The purpose of this study was to prepare microcapsules of VAP using combination maltodextrin and modified starches. Emulsion of VAP was prepared using cremophore RH 40 with Tween 80 in a homogenizer and formed emulsion was spray-dried. The spray process was optimized using a central composite design for two variables to obtain microcapsules with desirable characteristics. Microcapsules containing 30% of VAP were produced using different concentration of wall materials. The prepared microcapsules were evaluated for their physical, morphological, in-vitro drug release and SEM study. The results showed that obtained microcapsules are nearly spherical in shape with a particle size ranged from 1 to 12 μm. The drug content and encapsulation efficiency (53% - 63%) of different batches were found within acceptable range. These stabilized drug loaded microcapsules were incorporated into silicone cream based formulation for convenient topical application and evaluated for its physicochemical parameters. The drug release study showed 80.18% to 83.43% of drug release from VAP microcapsules while topical formulations prepared by VAP microcapsules showed 67.09% to 71.45% drug release at the end of 24 hrs. The formulations were kept for 3 months stability study as per ICH guidelines and found to be stable.

关键词： Vitamin A Palmitate Microencapsulation Spray drying Starch derivatives Topical delivery

Copper Salt of 12-Tungstophosphoric Acid： An Efficient and Reusable Heteropoly Acid for the Click Chemistry

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Chinese Journal of Chemistry 2013年第4期31卷 534-538页

作者： K. V. purnima d. Sreenu N. Bhasker K. Nagaiah N. Lingaiah B. V. Subba Reddy J. S. Yadav division of Organic Chemistry Indian Institute of Chemical Technology Hyderabad 500 007 India division oflnorganie and Physical Chemistry Indian Institute of Chemical Technology Hyderabad 500 007 India

Three components coupling of alkyl bromide, sodium azide and alkyne has been achieved using a catalytic amount of copper-exchanged phosphotungstic acid （Cu-TPA） in the presence of triethyl amine in dMF to afford substituted triazoles in good yields with high selectivity. Interestingly, the coupling of alkyl azide with alkyne pro- ceeds readily at room temperature to furnish 1,2,3-triazoles in excellent yields. The catalyst can be recovered and reused for three to four subsequent runs with a minimal decrease of activity. The use of copper modified heter- opolyacids makes this procedure simple, convenient and environmentally friendly.

关键词： Cu-exchanged heteropoly acids click reaction three-component reactions triazoles