Thermal, spectroscopic, and dissolution studies of the simvastatin–acetylsalicylic acid mixtures

The objective of the present investigation was to study the effect of eutectic formation on in vitro dissolution of simvastatin (SIM) released from mixtures with acetylsalicylic acid (ASA) prepared by a grinding method. SIM–ASA mixtures were characterized by means of differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray powder diffractometry (XRPD), and in vitro dissolution tests. IR spectroscopy and XRPD studies indicated no interaction between SIM and ASA in the solid state. The DSC investigation has revealed that SIM and ASA form a simple eutectic system containing 66.6 % w/w of SIM at the eutectic point. In vitro dissolution studies of SIM and its mixtures with ASA were carried out. The eutectic mixture shows an appreciable increase in the dissolution rate in comparison with other ratios and SIM in 0.5 % w/v sodium lauryl sulfate. The dissolution enhancement of SIM was related to the effective wetting of the drug particles with a significantly reduced size released from eutectic composition. In conclusion, dissolution of SIM can be enhanced through eutectic formation with ASA by means of simple mechanical activation (a grinding method).     

Thermal,spectroscopic, and dissolution studies of ketoconazole–Pluronic F127 system

One strategy for improving the dissolution of poorly water soluble drugs is to prepare solid dispersions such as binary mixtures with hydrophilic carriers. These mixtures are generally characterized by better solubility than those of the individual components from which they are formed. In the present study, solid dispersions of ketoconazole (KET) with Pluronic F127 (PLU) were prepared by the grinding method. Solid–liquid equilibria in the system being studied were investigated by differential scanning calorimetry. A phase diagram for the whole range of compositions was constructed. The investigation revealed that ketoconazole and Pluronic F127 form a simple eutectic system containing 4.4 % w/w of ketoconazole at the eutectic point. The results of Fourier transform infrared spectroscopy and X-ray powder diffractometry studies of obtained mixtures suggest that there is no drug-carrier interaction and both components are crystalline in the solid dispersion with the whole range of composition. The prepared mixtures show an appreciable improvement of the dissolution rate of KET in 0.5 % w/v sodium lauryl sulfate. The improvement of the dissolution rate of drug is additionally increased by effective solubilization.     

High-throughput synthesis and characterization of bulk ceramics from dry powders

A high-throughput experimental (HTE) setup using conventional powders as raw materials was developed to synthesize and characterize ceramic bulk samples avoiding the customary liquid- or vapor-phase synthesis routes. Its functionality was verified using the well-known binary material system ZrO2-Y2O3. Libraries of 0.5 mol % yttria resolution were prepared using varying boundary systems as well as a number of liquid mixing aids. Automated powder X-ray diffraction (XRD) was applied to check the monoclinic phase content retained after heat-treatment on various positions for each sample. This phase information was used for comparison with a reference library comprising conventionally prepared samples by means of a regression analysis and mean deviation of monoclinic phase percentage. Out of the eight HTE libraries, three showed a significant comparability to the reference library.     

Application of a new mathematical method for the estimation of the mean surface area to calculate the percolation threshold of lobenzarit disodium [correction of dissodium] salt in controlled release matrices

One of the practical handicaps for the application of the percolation theory to estimate the percolation threshold of drugs in controlled release systems is the fact that the dissolution studies must be carried out so that only one surface of the tablet is exposed to the dissolution medium. The aim of this work is to estimate the percolation threshold of the antiarthritic drug lobenzarit dissodium (LBD) in inert matrices prepared with the excipients Ethocel((R)) 100 and Eudragit((R)) RS-PO (10-75% w/w). Release assays were performed using the paddle method. The whole surface of the tablets was exposed to the dissolution medium. For the first time, a new mathematical method is developed to transform the amount of drug released in amount released per surface area in order to calculate the percolation thershold of LBD. The mathematical method proposed allows to calculate, using a new equation, the evolution of the mean surface area (O((t))). The new method was validated and three novel results were achieved: A constant value of (O((t))) at critical time (theta) in the matrices (O((theta))=1.272 cm(2)); a linear relationship between initial surface area (O((0))) and critical time; and a linear relationship between O((t)) and time. Employing the values of O((t)), it was possible to calculate for the first time, the percolation threshold (p(c1)) for LBD in Ethocel((R)) 100 (p(c1)=0.280+/-0.102) and Eudragit((R)) RS-PO (p(c1)=0.344+/-0.07) matrices.     

Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation,hardness and storage on in vitro release kinetics

The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.     

Immediate release tablets of telmisartan using superdisintegrant-formulation, evaluation and stability studies

Telmisartan (anti-hypertensive) is insoluble in water; hence the drug may be slowly or incompletely dissolved in the gastro intestinal tract. So the rate of dissolution and therefore its bioavailability is less (bioavailability 42%). In the present study an attempt has been made to prepare immediate release tablets of telmisartan by using Polyplasdone XL-10 (Crosspovidone) at intragranular, extragranular and partly intra and extragranular level of addition to increase the rate of drug release from dosage form to increase the dissolution rate and hence its bioavailability. The prepared granules and tablets were evaluated for their physiochemical properties and in-vitro dissolution study was conducted for the prepared tablets. It was concluded that the immediate release tablets with proper hardness, disintegration time and with increase rate of dissolution can be made using Polyplasdone XL-10. Formuation-10 (F10) was selected for stability study and the in-vitro dissolution study showed that was no difference in percent of drug released between initial and sixth month sample.     

Improvement of the dissolution rate of nitrendipine using a new pulse combustion drying method

Solid dispersions (SDs) of nitrendipine (NTD), a poorly water-soluble drug, were prepared with the Hypulcon pulse combustion dryer system, and the physicochemical properties of particles were investigated and compared with those of particles prepared with a spray dryer. The SD particles prepared with Hypulcon using Aerosil and Tween 80 as carriers showed improved properties over those prepared with a conventional spray dryer, such as smaller particle size, tighter particle size distribution, and no agglomeration. Powder X-ray diffraction and differential scanning calorimetry evaluation showed that the drug in the NTD-Aerosil SD prepared with 5% (v/v) Tween 80 solution was dispersed in an amorphous state. Fourier transformation IR spectroscopy indicated the presence of hydrogen bonds between NTD and Aerosil. Aerosil had greater ability to improve the dissolution of NTD than Sylysia and other polymers. The highest drug supersaturation concentration was maintained continuously during the dissolution test of the NTD-Aerosil SD prepared with 5% (v/v) Tween 80 solution using Hypulcon. The good hydrophilicity and dispersibility of Aerosil, solubilization of Tween 80, and actions of shock waves and ultrasonic waves might account for the amorphization of NTD and improved dissolution rate of SDs. Pulse combustion drying with low drying costs and high thermal efficiency is a promising method for the preparation of SD particles with improved properties without using organic solvent.     

Preparation and characterization of cyclodextrin inclusion complex of naringenin and critical comparison with phospholipid complexation for improving solubility and dissolution

Naringenin, a flavonoid specific to citrus fruits shows a variety of therapeutic effects like anti-inflammatory, anticarcinogenic, and antitumour effects. But it is associated with some limitations like poor water solubility, poor dissolution, lower half-life, and rapid clearance from the body. With the aim of improving amorphous nature, water solubility, and dissolution profile of naringenin and its complexes were prepared with β-cyclodextrin in three different molar ratios (1:1, 1:2, and 1:3) by solvent evaporation method. These complexes were characterized for solubility, drug content, chemical interaction (using FTIR), phase transition behavior (using DSC), crystallinity (using XRPD), surface morphology (using SEM), and in vitro dissolution study. The results were also critically compared with the results obtained from naringenin-phospholipid complexes (from author’s previous study). The prepared complexes showed high drug content (ranging from 69.53 to 84.38 %) and about two fold improvement in water solubility (from 41.81 to 76.31 μg mL^?1 in the complex with 1:3 ratio). SEM of the complexes showed irregular and rough surface morphology. FTIR, DSC, and XRPD data confirmed the formation of the complex. Unlike the free naringenin which showed a total of only 48.78 % drug release at the end of 60 min, the complex showed 98.0–100 % in dissolution study. Thus it was concluded that the β-cyclodextrin of naringenin may be of potential use for improving bioavailability of poorly soluble phytoconstituents/herbal drugs. On critical comparison with the phospholipid complex of naringenin both the techniques were found almost equally effective in improving the solubility and the dissolution performance of naringenin in the complex form.     

Crystallisation of zeolite mordenite and ZSM-5 without the aid of a template

A complex of tenoxicam with-cyclodextrin was prepared by using co-grinding and freeze drying methods. The resulting products were studied by the solubility method, ultraviolet and infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry. The dissolution behaviour of the products was also examined. The dissolution rate of the co-ground and freeze-dried products was faster than that of the pure drug and the physical mixture of drug and-cyclodextrin. The enhanced dissolution rate of the products might be attributed to the amorphous state, the increased wettability of the drug and the inclusion complex formation.     

Dissolution enhancement of quercetin through nanofabrication, complexation, and solid dispersion

The main aim of this study was to enhance the dissolution rate of a poorly water-soluble antioxidant drug, quercetin, by fabricating its nanoparticles, complexes and solid dispersions using evaporative precipitation of nanosuspension (EPN). We studied the influence of the type of antisolvent, drug concentration and solvent to antisolvent ratio on the quercetin particles formed during EPN. With water as antisolvent, the particles were big, irregular and flake type but with benzene or hexane as antisolvent, the particles were smaller and needle type. Smallest particles of 220 nm diameter were achieved with hexane as antisolvent, lowest drug concentration and highest solvent to antisolvent ratio. The relative dissolution values showed that the dissolution rate of the EPN prepared quercetin nanoparticles was much higher than that of the raw drug. Quercetin formed inclusion complexes with β-cyclodextrin, and solid dispersions with polyvinylpyrrolidone and pluronic F127, where quercetin was present in an amorphous form and/or was dispersed at a molecular level. The dissolution rate of quercetin in its complexes and solid dispersions improved significantly from the raw quercetin as indicated by the percent dissolution efficiency. It was interesting to note that at lower carrier concentration, the solid dispersions of quercetin with polyvinylpyrrolidone and pluronic F127 presented better dissolution than its complex with β-cyclodextrin but at higher carrier concentration, there was no significant difference in the dissolution behavior of the three formulations. Using Korsmeyer-Peppas model, diffusion was found to be the main release mechanism.     

Enhanced poling efficiency in rigid-flexible dendritic nonlinear optical chromophores

Naringenin is a flavonoid specific to citrus fruits and possesses anti-inflammatory, anticarcinogenic, and antitumour effects. But due to a lower half-life and rapid clearance from the body, frequent administration of the molecule is required. To improve the bioavailability and prolong its duration in body system, its phospholipid complexes were prepared by a simple and reproducible method. Naringenin was complexed with phosphatidylcholine in equimolar ratio, in presence of dichloromethane. The prepared Phytosomes (naringenin–phospholipid complex) were evaluated for various physical parameters like FT-IR spectroscopy, Differential Scanning Calorimetry (DSC), X-ray powder diffractometry (XRPD), Solubility, Scanning Electron Microscopy (SEM) and the in vitro drug release study. These phospholipid complexes of naringenin were found to be irregular and disc shaped with rough surface in SEM. Drug content was found to be 91.7% (w/w). FTIR, ¹H NMR, DSC and XRPD data confirmed the formation of phospholipid complex. Water solubility of naringenin improved from 43.83 to 79.31 μg/mL in the prepared complex. Unlike the free naringenin (which showed a total of only 27% drug release at the end of 10 h), naringenin complex showed 99.80% release at the end of 10 h of dissolution study. Thus it can be concluded that the phospholipid complex of naringenin may be of potential use for improving bioavailability.     

Preparation of polyurethane elastomers (PUEs) in a high‐throughput workflow

High‐throughput experimentation (HTE) represents a promising and versatile approach for polyurethane (PU) research as a tool to rapidly screen and characterize a large number of samples in an automated way. To realize a unique HTE workflow for the research and development of PU elastomers (PUEs), the use of parallel automated formulation and coating platforms at Flamac were explored. To evaluate the applicability of HTE for PUEs, four different PU systems were investigated with different reactivities and viscosities. All prepared PUEs were evaluated by conventional physical testing methods measuring the E‐modulus, tensile‐elongation and the hardness properties revealing similar trends as conventionally prepared PUEs indicating the viability of the HTE approach. In addition, the properties of the PUEs were also investigated using downscaled microtensile bars as well as depth‐sensing indentation, again, revealing similar trends. With this proof of principle study, we demonstrated for the first time that HTE can also be extended to polymeric materials based on high reactive and viscous raw materials in combination with complex technologies. The reported results provide a basis for the use of HTE approaches for preparing, screening and characterizing large numbers of PUEs for R&D purposes. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crospovidone

We attempted the development of rapid oral disintegration tablets by direct compression using co-ground mixture of D-mannitol and crospovidone. The co-ground mixture was prepared with a vibration rod mill. The tablets were formed by compression using a single punch-tableting machine after addition of the co-ground mixture to non-ground D-mannitol, crospovidone and magnesium stearate. Regarding the properties of tablets, hardness and the time of disintegration were measured. The particle diameter and specific surface area of the co-ground mixture were measured. The tablets manufactured from a physical mixture of 30% (w/w) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9 :1) with 65.5% (w/w) of non-ground mannitol, 4% (w/w) of crospovidone, and 0.5% (w/w) of magnesium stearate had good properties for rapidly disintegrating tablets in the oral cavity. They showed the hardness of 4.9 kg and disintegration time of 33 s. We found that adding co-ground mixture of D-mannitol and crospovidone is useful in enhancing hardness of the tablets that could not be achieved by addition of their individually ground mixture. The improvement in the hardness of the tablets was also observed when other saccharides and disintegrants were used. This method was proved to be applicable in the manufacture of tables of ascorbic acid, a water-soluble drug and nifedipine, a slightly water soluble drug; and the dissolution rate of nifedipine from the tablets in water was remarkably improved. The particle sizes of D-mannitol in the co-ground mixture were smaller than that of the individually ground mixture, resulting in a larger specific surface area of the co-ground mixture than that of the individually ground mixture. Therefore, it was presumed that crospovidone acted as a grinding assistant for D-mannitol in the co-grinding process, enhancing the hardness of tablets by increasing the contact area among powder particles.     

Preparation of ultrafine fast-dissolving feruloyl-oleyl-glycerol-loaded polyvinylpyrrolidone fiber mats via electrospinning

Fast-dissolving drug delivery membranes for poorly water-soluble drugs were prepared by electrospinning using feruloyl-oleyl-glycerol (FOG) as a model drug and polyvinylpyrrolidone (PVP) K90 as a polymer matrix in a mixed solvent of chloroform/ethanol (4:1, v/v). Results from Fourier-transform infrared spectroscopy (FT-IR) illustrated good compatibility between FOG and PVP as well as a good distribution of FOG within the fibers. The morphology and diameter of the fibers were influenced by the concentration of PVP and the applied voltage. When the PVP concentration was 5% (w/v) and the applied voltage was 14 kV, uniform and smooth fibers were obtained, with diameter 700-800 nm. Wetting time assays confirmed fast-dissolving properties with the average dissolution time for FOG-loaded PVP fiber membranes being 2.0±1.5 s. These results demonstrate the potential of electrospinning solid dispersions to improve the dissolution profile of poorly water-soluble drugs.     

Application of electron probe micro-analysis to the estimation of chlorine in alumina-based heterogeneous catalysts

Chlorine in alumina-based catalysts has been determined with a scanning electron microscope attached to an energy dispersive x-ray analyser (SEM-EDX). The method is less time consuming compared to conventional methods involving sample dissolution followed by titrimetry, absorption spectrophotometry or ion chromatography. The spectrometer is calibrated with laboratory prepared standards. This technique is found suitable for the estimation of chlorine in the range 0.1-1.0% (w/w) with a relative standard deviation < 10% for chlorine levels above 0.2%     

Preparation, characterization and in vivo evaluation of antihyperglycemic activity of microwave generated repaglinide solid dispersion

The influence of microwave technology on the in vitro dissolution rate and in vivo antihyperglycemic activity of a poorly water soluble drug, repaglinide (RG) was studied. Solid dispersions were prepared by conventional fusion method and microwave method using poloxamer 188. The dispersions were characterized by solubility study, dissolution study, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Microwave generated solid dispersions exhibited remarkable improvement in solubility and dissolution rate compared to that of pure RG. Results of DSC, XRD and SEM study showed conversion of crystalline form of RG to amorphous form. In vivo studies revealed that the microwave generated solid dispersion showed significant improvements in antihyperglycemic activity as compared to RG alone, thus confirming the advantage of improved pharmacological activity of RG by microwave method. In conclusion, microwave method could be considered as simple, efficient and solvent free promising alternative method to prepare solid dispersion of poorly water soluble drug RG with significant enhancement in solubility, dissolution rate and antihyperglycemic activity.     

Formulation and evaluation of thermoreversible,mucoadhesive in situ intranasal gel of rizatriptan benzoate

The present study was aimed to formulate and evaluate in situ thermoreversible intranasal gel of an antimigraine drug rizatriptan benzoate. The poloxamer 407 and carbopol 934 were used as thermoreversible and mucoadhesive polymers respectively. The gels were prepared with cold method. The phase transition temperature was determined with visual method. The gels were evaluated for their pH, mucoadhesive strength, in vitro release and ex vivo drug permeation through goat nasal mucosa. The histopathological study of the nasal mucosa was carried out to check for its damage during drug permeation. The 18 % w/v poloxamer solution was found to be showing phase transition at physiologic conditions (34–35 °C). As the percentage of carbopol 934 was increased from 0.1 to 0.5 % w/v the gelling temperature was found to be decreased. All formulations were showing mucoadhesive strength above 4,000 dynes/cm². Drug permeation studies have indicated that the drug permeation rate can be increased by using carbopol 934 above 0.3 % w/v concentration. The histopathological evaluation of nasal mucosa after drug permeation study has not shown any evidence of damage. Thus in situ thermoreversible mucoadhesive gel of rizatriptan benzoate can be a promising approach to treat migraine.     

Solubility, dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique

The objective of present work was to enhance the solubility and bioavailability of poorly aqueous soluble drug Irbesartan (IBS). The solid dispersions were prepared by spray drying method using low viscosity grade HPMC E5LV. Prepared solid dispersions were characterized by dissolution study, fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD). Results of the SEM, DSC and XRD study showed the conversion of crystalline form of IBS to amorphous form. The dissolution rate was remarkably increased in case of solid dispersion compared to pure IBS. Solubility and stability of solid dispersion was increased due to surfactant and wetting property, slowing devitrification and having anti-plasticization effect of HPMC E5LV. In vivo studies were performed in healthy rabbits (New Zealand grey) and compared with plain IBS. Solid dispersions showed increase in relative bioavailability than the plain IBS suspension. In conclusion, the prepared solid dispersions showed remarkable increase in solubility, dissolution rate and hence bioavailability of poorly water soluble drug Irbesartan.     

Study of the critical points in lobenzarit disodium hydrophilic matrices for controlled drug delivery

Percolation theory is a multidisciplinary theory that studies chaotic systems. It has been applied in the pharmaceutical field since 1987. The application of this theory to study the release and hydration rate of hydrophilic matrices allowed for first time to explain the changes in release and hydration kinetic of swellable matrices type controlled delivery systems. The objective of the present paper is to estimate the percolation threshold of HPMC K4M in matrices of lobenzarit disodium and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The materials used to prepare the tablets were Lobenzarit disodium (LBD) and HPMC of viscosity grade K4M. The drug mean particle size was 42+/-0.61 mum and the polymer was sieved and 150-200 microm granulometric fraction was selected. The formulations studied were prepared with different excipient contents in the range of 10-80% w/w. Dissolution studies were carried out using the paddle method and the water uptake measurements were performed using a modified Enslin apparatus. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. According to percolation theory, the critical points observed in dissolution and water uptake studies are attributed to the existence of an excipient percolation threshold. This threshold was situated between (18.58 to 24.33% v/v of HPMC). Therefore, the LBD-HPMC K4M matrices with a relative HPMC particle size of should be formulated with an excipient content above 24.33% v/v of HPMC, to obtain a control of the drug release from these systems.     

Preparation & characterization of embelin�Cphospholipid complex as effective drug delivery tool

The aim of the present study was to prepare an embelin?Cphospholipid complex (EPC) formulation in an attempt to enhance the water solubility and to characterize the new developed formulation. Embelin, due to water insolubility causes poor bioavailability by oral route. To improve the bioavailability and prolong its duration in body system, its phospholipid complexes were prepared by a simple and reproducible method. EPC was formulated by mechanical dispersion method using ethanol as a reaction medium, embelin and phospholipids were dissolved into the medium, after that organic solvent was removed under vacuum condition and EPC was formed. The complex formation was confirmed by carrying out FTIR, ¹H-NMR, XRD, DSC and microscopical studies. Solubility and in vitro studies were carried out to ascertain the solubility and dissolution pattern of free and complexed embelin. Content of embelin in EPC was found to be 92.44% (w/w). FTIR, ¹H NMR, DSC and XRD data confirmed the formation of embelin phospholipid complex. Water solubility of embelin was improved from 3 to 42 ??g/mL in the prepared complex. n-Octanol solubility were also altered for free embelin and EPC from 2.3 to 39 ??g/mL. Unlike the free embelin, which showed a total of only 19% drug release at the end of 120 min, EPC showed 99.80% release at the end of 120 min of dissolution study in distilled water. Microscopical characterization of the developed formulation also showed the entrapment of embelin in the lipid core showing complex structure, which was further, supported by change in surface morphology of embelin on microscopical examination. Hence, the present findings demonstrate that complexing embelin with phospholipid can be further explored for improved therapeutic implications.