Preparation and characterisation of lornoxicam solid dispersion systems using hot melt extrusion technique

Ritesh Fule,Tarique Meer,Purnima Amin,Dinesh Dhamecha,Shyam Ghadlinge 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.1

The aim of the research study was to investigatethe ability of Soluplus and surfactant individually aswell as in combination to improve the solubility, subsequentlythe dissolution profile of lornoxicam (LORX). Alaboratory size single screw rotating extruder with temperatureand speed control parameters employed during hotmelt extrusion (HME) processing of LORX along withpolymer-surfactant blends. Soluplus used as primarysolubilizing agent for preparing solid dispersion (SD). Along with Soluplus different concentrations of surfactantssuch as PEG 400, Lutrol F127, Lutrol F68 were usedto solve the permeability issues related to LORX. Encapsulationof LORX particles inside the molten matrix ofpolymer-excipient blend was confirmed by DSC, XRD andFT-IR. Drug excipient microscopic interaction was furtherconfirmed by scanning electron microscopy (SEM). Depending upon the ratio of the polymer and surfactantsused, the solubility of the hot melt extruded LORX wasimproved and found to be in the range 35–86 lg/ml (actualaqueous solubility of LORX was found to be 0.0083 lg/ml). Dissolution profile of the extruded SD was improvedand was found to be in the range of 98–104 % within20 min (actual dissolution profile of LORX was found tobe 8 % at the end of 1 h). SEM and Raman images suggestthe formation of amorphous dispersion systems. SD wassubjected to stability studies as per ICH guidelines andfound to be stable after 6 months when analyzed by HPLC. SD prepared from HME significantly improves the solubilityand dissolution profile of LORX—a BCS class IIdrug.

Preparation and characterizations of stable amorphous solid solution of azithromycin by hot melt extrusion

Divakar R. Jaiswar,Purnima D. Amin,Durgesh Jha 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.7

In the present study aim was to prepare stable solid solution azithromycin dihydrate (AZI) by hot melt extrusion technology (HME). Soluplus and Kollidon VA 64 were selected among polymers based on Hansen solubility parameter calculation in order to prepare amorphous of AZI. Further physicochemical properties of extrudates were characterized by DSC, FTIR, XRD, SEM and contact angle measurement. DSC revealed single broad endothermic peak in extrudates indicated miscibility of AZI into polymeric carriers, which formed monophasic solid system termed as solid solution. XRD confirmed amorphous nature of AZI in extrudates. DSC and XRD suggested molecular dispersion of AZI in polymeric carriers. Amorphous AZI exhibited statistically significant high solubility (P\0.0001) in water in comparison with pure AZI. Solid solution batch AZI 03 showed significant enhancement in solubility (P = 0.0004) in pH 6. The dissolution in dissolution medium pH 6 and water resulted in statistically significant differences (P\0.05) in the percentage amorphous AZI dissolved compared to the percentage AZI dissolved over the period of 60 min. Solid solution formulation showed better wettability than that of pure AZI. Amorphization and increased wettability attributed to solubility and dissolution rate enhancement. Assay and amorphous solid solution characteristics of AZI were found to be stable under accelerated storage condition as per ICH guideline for a period of six months. Therefore, hot melt extrusion technology was suitable method to prepare stable solid solution and dissolution rate enhancement for poorly soluble active like AZI.

Preparation and evaluation of carbamazepine loaded fibrous electrospun mats of starch

Tarique Ali Meer,Mirza Shehzad Baig,Purnima D. Amin 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.3

The preset work deals with preparation of fibrous electrospun mats of starch (FEMOS) carrier, from naı¨ve starch, through a process of electrospinning. The developed FEMOS was explored for the solubility enhancement of poorly water soluble drug carbamazepine. Solid state characterization was performed with respect to Fourier transform infra-red spectroscopy, X-ray diffraction, scanning electron microscopy, contact angle determination, dissolution kinetics, and differential scanning calorimetry. Rapid release profiles were observed when the carbamazepine was loaded on FEMOS. This effect may be due to high surface area, improved wettability and reduced crystallinity of the loaded drug on FEMOS. The developed formulation was found to have a similar in vivo performance as compared to marketed formulation TegretolⓇ.

Solubility and dissolution rate enhancement of lumefantrine using hot melt extrusion technology with physicochemical characterisation

Ritesh Fule,Tariq Meer,Ajay Sav,Purnima Amin 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.4

The interest in hot-melt extrusion as a drug delivery technology for the production of solid dispersion is growing rapidly. Lumefantrine (LUMF) is an antimalarial drug that exhibits poor oral bioavailability, in consequence of its poor aqueous solubility. To improve its antimalarial activity, solid dispersion formulation using hot melt extrusion technology was prepared. Appropriate selection of polymers, favoured the production of amorphous LUMF-polymer solid dispersions. The physicochemical properties of solid dispersions were characterized using scanning electron microscope, Infrared spectroscopy,differential scanning calorimetry and X-ray diffraction. LUMF SD showed enhanced dissolution rate attributed to amorphosization of LUMF. The IC50 value of LUMF SD formulations was found to be (0.084–0.213 ng/mL) i.e. 220–101 times lower than the IC50 value of pure LUMF (18.2 ng/mL) and 45–18 times lower than the IC50 value of standard antimalarial drug, chloroquine (3.8 ng/mL). Molecular dynamic simulation approach was used to investigate drug-polymer molecular interaction using computational modelling Schrodinger software. LUMF SD powder makes the Coartem therapy more operative with value-added beneficial comeback.

Enhanced solubility and dissolution of simvastatin by HPMC-based solid dispersions prepared by hot melt extrusion and spray-drying method

Sharadchandra Dagadu Javeer,Rahul Patole,Purnima Amin 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.6

The objective of this study was to use low viscosity grade hydroxypropyl methyl cellulose (Methocel E3 LV and Methocel E5 LV) to enhance the solubility and dissolution of poorly water soluble drug simvastatin (SIM). Two different technologies, hot melt extrusion and spray drying were employed. Characterization of hot melt extrudes and spray dried samples was done by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction studies and scanning electron microscopy. The result of the study showed the conversion of crystalline form drug into amorphous form indicating increase in dissolution rate and solubility of SIM.

Solubility modulation of bicalutamide using porous silica

Tarique Meer,Ritesh Fule,Deepak Khanna,Purnima Amin 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.4

Objective of the present study was to explore the potential of porous silica (AEROPERL 300 Pharma)in modulating dissolution kinetics of poorly water soluble drug bicalutamide (BCL). The drug release from the developed formulation was found to be significantly higher as compared to neat BCL. This improved release kinetics of BCL may be attributed to high surface area, improved wettability and decreased crystallinity. Solid state characterization of the developed formulation was carried out with respect to IR, XRPD, SEM, DSC and dissolution. The proposed system showed a significant capability for the solubility enhancement of BCL. The dissolution profile from BCL-AEROPERL 300 Pharma (AP) system was fitted into various drug release kinetics models, in order to understand the BCL release mechanism.

Synthesis and evaluation of octenyl succinate anhydride derivative of fenugreek gum as extended release polymer

Ajay Kumar Sav,Ritesh Amol Fule,Meer Tarique Ali,Purnima Amin 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.5

In current study, fenugreek gum (FG) plant derived product was investigated as a release retarding polymer. The octenyl succincate anhydride derivative of fenugreek gum (OSFG) was synthesized to introduce hydrophobic property and investigated for its drug release retarding property with reference to FG. The reaction was carried out in anhydrous conditions at different temperature (40–98 C) using NaHCO3 as a mild base catalyst and the influences of three factors such as reagent/substrate concentration,reaction temperature and time on the degree of substitution of OSFG were studied. Highly water-soluble metoprolol succinate (MPS) and poorly water-soluble carbamazepine (CBZ) were selected as model drug as for release studies. It was observed that increase in reaction temperature and reagent concentration resulted in high degree of substitution with significant decrease in viscosity. Reaction carried out at 98 C for 2 h showed high degree of substitution (0.133) with moderate retention of viscosity compared to plain FG. FTIR, DSC, XRD, solid state CPMAS 13C-NMR, and SEM studies provide structural information of synthesized OSFG. MPS ER tablet prepared with drug:OSFG:FG at the weight of 1:4:2 and CBZ ER tablet with drug:OSFG at the weight ratio of 1:3, respectively. Both formulations showed similar drug release profile compared to marketed formulations. Optimized tablet formulations were found to be stable under stability condition according to ICH guidelines. It was concluded that the developed formulations with OSFG have a release retarding property and can be used alone or in combination with other polymers for a controlled release.

Formulation of highly purified fenugreek gum based silica lipid drug delivery system for simvastatin with enhanced dissolution rate and in vitro characterization

Ajay Kumar Sav,Meer Tarique Ali,Ritesh Amol Fule,Purnima Dhanraj Amin 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.5

In current study, highly purified fenugreek gum (HPFG) isolated by patented method explored as emulsifier and hydrophilic solid carrier in drug delivery system. Antihyperlipidemic drug simvastatin (SIM) was selected as drug model for the study as it is associated with poorly water solubility and low bioavailability problems (\5 %). A suitable HPFG-based silica lipid system composed of SIM (1.5 %), medium chain triglyceride Capmul MCM (10 %) as lipid phase, 0.6 % HPFG as emulsifier and HPFG 2.5 %, different grades colloidal silica (7.5 %)(Aerosil 300 Pharma, Aerosil 380 Pharma and Aeroperl 300 Pharma) as hydrophilic solid carriers was developed. The optimized HPFG-based silica lipid systems were characterized for physical characteristics like flow ability,compressibility, redispersiblity, solubility and in vitro drug release using USP apparatus II in pH 6.8 phosphate buffer. The system was also characterized for Fourier transform infrared spectroscopy, powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The developed formulation was found to have excellent flow property, readily redispersiblity, better aqueous solubility and showed 3–4-fold increase in dissolution rate as compared to plain drug and marketed formulation (Simlo 10). Transition of crystalline drug to amorphous state was confirmed by DSC,PXRD and SEM studies. Enhanced dissolution rate and solubility possibly attributed to improved wetting, amorphous drug state and facilitated diffusion from lipid-based system. Thus developed HPFG-based silica lipid system provides an alternative means for SIM with enhanced dissolution rate and stability in oral solid dosage form.

Encapsulation of vitamin E acetate to convert oil to powder microcapsule using different starch derivatives

Avinash Bhaskar Gangurde,Meer T. Ali,Jaywant N. Pawar,Purnima Dhanraj Amin 한국약제학회 2017 Journal of Pharmaceutical Investigation Vol.47 No.6

Vitamin E (VE) is highly lipophilic in nature with a very low water solubility which degrades rapidly in presence of oxygen, and free-radical mediated oxidative processes. Spray drying of oil-in-water emulsions containing hydrophilic carriers was used to encapsulate lipophilic compounds into powders. The purpose of this study was to prepare microcapsules of VE using different starch derivatives to increase its stability and to disperse it in aqueous environment. Emulsion of VE acetate was prepared using cremophore RH 40 with tween 80 in a homogenizer and then spray dried. The spray process was optimized using a central composite design for two variables to obtain microcapsules with desirable characteristics. Microcapsules containing 2, 4 and 6% w/w of VE acetate were produced. The microcapsules were evaluated for their physical, morphological, in vitro release, solid state characterization such as SEM, FTIR, P-XRD and its in vitro free radical scavenging activity. The results showed that obtained microcapsules are nearly spherical in shape with mean particle size of microcapsules were ranged from 1 to 12 lm. The drug content and encapsulation efficiency (53–63%) was found to be uniform and within acceptable range. Optimized formulations were kept for 3 months stability study and found to be stable.

Microencapsulation using aqueous dispersion of lipid matrix by fluidized bed processing technique for stabilization of choline salt

Avinash B. Gangurde,Ritesh A. Fule,Sharadchandra D. Javeer,Rahul K. Patole,Jaywant N. Pawar,Purnima D. Amin 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.2

Choline bitartrate (CBT) is a water solubleessential nutrient belongs to vitamin-B family. It is moisturesensitive in nature and marketed formulation has stabilityrelated problems during storage which curtails itseffectiveness. Waxes such as hydrogenated soya bean oil(HSO) reported to be an excellent coating carrier to reducemoisture sensitivity or hygroscopic nature of drug candidates. However, literature dictates HSO applications hasbeen explored mostly using non-aqueous methods or hotmelt techniques of formulation development. In this work,microparticles of choline bitartrate with aqueous coatingdispersion of HSO as primary carrier was successfullydeveloped using fluidized bed coating technique. Aqueousdispersion of HSO was prepared using selected binder in ahomogenizer and formed aqueous dispersion was thensprayed through 0.8 mm gun in fluidized bed processor. The microparticles were evaluated for parameters like flowproperties, morphological characteristics, drug content,encapsulation efficiency and drug release behaviour. Thesolid state characterization of optimized microparticlebased formulation was done by differential scanning calorimetry,X-ray diffractometry, infrared spectroscopy andscanning electron microscopy. The results showed thatmicroencapsulation of choline bitartrate were successfullydone by aqueous wax coating dispersion without using anyorganic solvent or hot melt techniques. Discolouration,fishy odour and drug content variation was not observedafter 6 months stability studies. Choice of proper carrier todrug ratio and selective formulation technique are criticalparameters for dispensing CBT microparticle based formulationwhich might significantly enhance itseffectiveness.