Change to the non-cross-linked DURO-TAK 87- 2510 reaches equilibrium after a shorter time, and to a lower value of saturationsolubility of the scopolamine at both 25 °C (Fig. 2 a) and 45 °C (Fig. 2 b). The rate of uptake of scopolamine into the acceptor at times up to 2 days is, however, the same with both polymers. With DURO-TAK 2510 this uptake is completed after 2 days, but with DURO-TAK2677 the uptake continues until equilibrium is reached at day 15. This indicates that the diffusivity of the scopolamine is similar in both polymers. The observed shorter time to reach equilibrium in DURO-TAK 2519 is just a result of the higher value of c s * that has to be reached.
release was done. The FTIR was used to confirm compatibility and to rule out any possible interactions between drug and carriers. The optimal nanosuspension was obtained with particle size of 510.4 nm, saturationsolubility of 557 μg/ml, zeta potential of - 4.49 mV, entrapment efficiency of 96.82%, and in-vitro drug release of 100.14%. Also, the optimal formulation was found to be stable in the accelerated conditions. Data of nanosuspensions were fit in to different equations and kinetic models and found to exhibit first order release kinetics with class II transport mechanism of diffusion. The scanning electron microscopy studies showed elongated nanoparticles with porous surface. The “Bottom up” method can be successfully employed to produce ezogabine nanosuspensions achieving reduced particle size and enhancing dissolution rate by increasing the saturationsolubility and remained stable at 25 °C.
Nanosuspensions are colloidal dispersions of nanosized drug particles stabilized by surfactants. They can also be defined as a biphasic system consisting of pure drug particles dispersed in an aqueous vehicle in which the diameter of the suspended particle is less than 1µm in size 7 . Reduction of drug particles to nanometer range leads to an enhanced dissolution rate not only because of increased surface area but also because of saturationsolubility. The increase in the saturationsolubility and solution velocity of nanoparticle is due to increase of vapour pressure of the particles. Nanosuspension have disclosed the problems associated with the delivery of poorly water soluble and poorly water and lipid soluble drugs and are unequalled because of their simplicity and rewards they confer over other strategies 8 . The particle size distribution of the solid particles in nanosuspensions is usually less than one micron with an average particle size ranging between 200 and 600 nm. An increase in the dissolution rate of micronized particles (particle size < 10 µm) is related to an increase in the surface area and consequently the dissolution velocity 9 . A Nanosuspension is a submicron colloidal dispersion of drug particles. A pharmaceutical
The pH of 1% solution was within 6 to 6.5 and 6 to 6.2, of DPH HCL and DPH tannate, respectively. The pH saturationsolubility profiles for DPH HCl and DPH tannate were showed significantly higher solubility of DPH HCl than DPH tannate at all the determined pH values and in water and organic solvents (Table 3). Both, drugs exhibited high solubility at a pH <2.0. For example, at room temperature, pH 1.2, the solubility of DPH HCl and DPH tannate were 107 and 34 mg/ml, respectively. However, the solubility of DPH HCl, being a weak base, demonstrated a parabolic relationship showing minimum solubility around pH 3.0 to 6.0 and high solubility in both the low acid and alkaline range, appears to dissolve maximally around pH ≤2.0. IR spectra of DPH salts (Þ g. 1) after stability study did not show any signiÞ cant changes in the characteristic peaks of DPH tannate, thus indicating good stability of drug at accelerated conditions and DPH HCl shows extra peak at 3600 to 3700 cm -1 indicating presence
Abstract: This study was aimed to enhance the dissolution rate, oral bioavailability and analgesic potential of the aceclofenac (AC) in the form of nanosuspension using cost-effective simple precip- itation–ultrasonication approach. The nanocrystals were produced using the optimum conditions investigated for AC. The minimum particle size (PS) and polydispersity index was found to be 112±2.01 nm and 0.165, respectively, using hydroxypropyl methylcellulose (1%, w/w), polyvi- nylpyrrolidone K30 (1%, w/w) and sodium lauryl sulfate (0.12%, w/w). The characterization of AC was performed using zeta sizer, scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The saturationsolubility of the AC nanocrystals was substantially increased 2.6- and 4.5-fold compared to its unprocessed active phar- maceutical ingredient in stabilizer solution and unprocessed drug. Similarly, the dissolution rate of the AC nanocrystals was substantially enhanced compared to its other counterpart. The results showed that .88% of AC nanocrystals were dissolved in first 10 min compared to unprocessed AC (8.38%), microsuspension (66.65%) and its marketed tablets (17.65%). The in vivo studies of the produced stabilized nanosuspension demonstrated that the C max were 4.98- and 2.80-fold while area under curve from time of administration to 24 h (AUC 0→24 h ) were found 3.88- and 2.10-fold greater when compared with unprocessed drug and its marketed formulation, respectively. The improved antinociceptive activity of AC nanocrystals was shown at much lower doses as compared to unprocessed drug, which is purely because of nanonization which may be attributed to improved solubility and dissolution rate of AC, ultimately resulting in its faster rate of absorption. Keywords: aceclofenac nanocrystals, precipitation–ultrasonication, dissolution rate, in vivo studies
The saturationsolubility studies were carried out for both the unprocessed pure drug and different batches of lyophilized nanosuspension.10mg of unprocessed pure drug and nanosuspension equivalent to 10 mg of silymarin was weighed and separately introduced into 25 ml stopper conical flask containing 10 ml distilled water. The flasks were sealed and placed in rotary shaker for 24 hours at 37°C and equivalent for 2 days. The samples were collected after the specified time interval and it is filtered and analyzed. The samples were analyzed using UV spectrophotometer at 287nm .
Nanosuspension is one of the most important strategies to enhance the oral bioavailability of poorly water soluble drugs 10 . Preparing nanosuspension can be a challenging technique. Various methods which are generally used to prepare nanosuspension are bottom-up including precipitation, and top-down including media milling, emulsion solvent diffusion method, supercritical fluid method, dry co-grinding, high- pressure homogenization, Nano edge 6, 11 . Nanosuspension have two particular advantageous properties, firstly increased saturationsolubility and secondly the enlarged surface. Both properties results in an increase in the dissolution rate according to the Noyes-Whitney Law 12 . In general it is advantageous to use nanoparticles that are as small as possible to achieve a maximum improvement in the oral bioavailability or a very rapid dissolution rate 13, 14 .
The saturationsolubility of Carbamazepine was determined by shaking method. Excess drug was added in 5 ml vial containing 2 ml distilled water and pH 7.4 phosphate buffer. After proper mixing of the mixture, the vial was kept in an orbital shaker at 37±1 0 C for 72 h to reach equilibrium. Then, the sample was removed and centrifuged at 3000 rpm for 15 min and filtered. Filtrate was suitably diluted and absorbance was taken at 284.0 nm using UV- Visible spectrophotometer. The solubility of drug was determined using standard calibration curve of drug in water and pH 7.4 phosphate buffer.
ABSTRACT: Improvement in the bioavailability of poorly soluble drugs is one of the challenges faced in the formulation development of the drugs. One of the most admirable and viable formulation approaches for this is self micro emulsifying drug delivery system (SMEDDS). A combination of clarithromycin and amoxicillin has been proved effective for treatment of H. pylori which are available only in tablet dosage form. Hence, the aim of the present study was to prepare SMEDDS of amoxicillin and clarithromycin for better patient compliance. SMEDDS were prepared using Peceol, Cremophor EL and Transcutol as oil, surfactant and co-surfactant respectively. Prepared SMEDDS were evaluated for particle size, zeta potential, water dispersion properties, saturationsolubility and in-vitro drug release. Dilution study by visual observation showed that there was spontaneous micro emulsification and no sign of phase separation. Study concluded that SMEDDS can be an effective alternative for tablet therapy with enhanced dissolution rate and bioavailability .
Enhancing permeability of poorly permeable drugs. (3) The therapeutic efficacy of a drug product intended to be administered by the oral route mainly depends on its absorption by the gastrointestinal tract. However, for a drug Abstract: Solid dispersions (SDs) are one of the most promising strategies used to improve the solubility of poorly water soluble drugs. This technology is mainly applied to improve the solubility of Class II and Class IV drugs. Bosentan monohydrate is an anti-hypertensive agent used in the treatment of pulmonary arterial hypertension, which has oral bioavailability of 40-50% and it belongs to the BCS class-II. Many attempts are made in the past to increase its solubility by preparing its solid dispersions. However, very few literature reports are available wherein polymers are used for preparation of solid dispersions. In the present work, an attempt is made to increase the solubility of bosentan by preparing its solid dispersions using polymer i.e. gelucire44/14 and poloxamer407 various techniques used for preparing Solid dispersions are by physical mixture, of solvent evaporation methods using different drug-polymer ratio. Thus prepared solid dispersions were evaluated for percentage yield, drug content, saturationsolubility and in-vitro dissolution studies. The result obtained from above studies indicated that, the solubility and dissolution of bosentan monohydrate of solid dispersions was improved as compared to pure drug by all the methods employed. Among various methods employed, solvent evaporation method produced good results compared to physical mixture, solvent method. Hence, Solid dispersion technology can be used to improve the solubility of bosentan monohydrate.
NTD drug was found to be faint yellow in color, odourless, crystalline solid and melting point 156- 160°C, which complies with E. P. limit. NTD nanocrystals were successfully prepared by the anti- solvent precipitation method. The obtained nanocrystals have been assessed for particle size analysis, zeta potential, saturationsolubility and solid-state characterisation by XPRD, DSC, FTIR and SEM analysis. Compatibility studies of NTD and excipients was conducted on FTIR studies. FTIR spectrums revealed that the fundamental peaks of the NTD were retained in the physical mixture indicating absence of any chemical interaction between them.
gm/mole. It is insoluble in water, freely soluble in methanol, soluble in diluted ammonia or sodium hydroxide. 1 According to the Biopharmaceutics Classification System (BCS) aqueous solubility and permeability are the most important variables affecting drug bioavailability. HCT is classified as Class IV, where the drugs have low solubility and low permeability characteristics after oral Abstract: Hydrochlorothiazide (HCT) is a class IV drug which has limited solubility and permeability, for overcome this problems co-crystallization method is used. Co-crystallization is the process to enhance the physical properties of drug molecule especially the solubility. HCT belongs to diuretic category and Propranolol Hydrochloride (PPL) belongs to Beta blocker category they are combined for use in tablet formulation. Co-crystallization was used to combine two drugs in single solid phase and thus to achieve new approach for combination therapy. Using the new approach co- crystals of PPL with HCT were prepared. Co-crystallization of two drugs were carried out by using solvent evaporation and solution co-crystallization method. The saturationsolubility was done to evaluate the solubility of co-crystals. Dissolution properties were determined and compared with the marketed tablet formulation. The prepared co-crystals has shown several times faster release than marketed tablet and optimized co-crystals were characterized by using DSC, FTIR and SEM.
optimization of the formulation variables such as concentration of poloxamer 407 and stirring time as independent variables. The particle size (PS) and maximum saturationsolubility (SS) were selected as dependent variables. Formulation thus optimized was subjected to in vitro dissolution test to evaluate improvement of dissolution in comparison to current marketed formulation of metaxalone, SKELAXIN ®
colored powder having very low solubility in water (21.12 mg/L). The main purpose of this study is to enhance the solubility of Ziprasidone HCl using lyophilisation technique. The β-Cyclodextrine and Hydroxy Propyl- β-Cyclodextrine were used as the water soluble carriers for increasing the solubility of Ziprasidone. All the inclusion complexes prepared by lyophilisation technique showed remarkable increase in the solubility compared to the pure Ziprasidone HCl. The saturationsolubility analysis demonstrated highest increase in the solubility of drug after complexation with HP-β-CD by lyophilisation technique. The inclusion complexes were characterized using DSC and XRD technique. During in vitro study result obtained that the lyophilized complexes with HPβ-CD showed 100% drug release within 10 min were as the lyophilized complexes with β– CD showed 100% drug release in 25 min. Therefore the freeze dried complex with HP-β-CD was selected for Catalepsy study on Wistar rats. In the catalepsy study the selected inclusion complex showed increase in bioavailability compared to the drug and almost all the data obtained from study was found to be 99.99% significant with the control . INTRODUCTION: 1-7 The way of treating
SaturationSolubility Studies: The solubility of Valsartan in different non-volatile liquid vehicles that are commonly used for the formulation of liquisolid com pacts, namely, propylene glycol, polyethylene glycol 200 (PEG 200), and PEG 400, Tween 20, Tween 40 and Tween 80 was determined by preparation of saturated solutions of the drug in these solvents and measuring the solubilized drug concentration. Excess Valsartan was stirred in the above mentioned solvents for 48 h at 25˚C. Accurately weighed quantities of the filtered supernatants were further diluted with methanol and analyzed spectrophotometrically at 250 nm for their drug content. From these results, the solubility of Valsartan in the respective liquid vehicle was calculated. Each experiment was carried out in triplicate 9, 10 .
all the solid dispersions as the ratio of carrier is increased. Highest solubility was observed with lipophilic carrier gelucire 44/14 and it was also observed that the solubility was slightly higher with solvent evaporation method than melting method. Table 12: Saturationsolubility studies of solid dispersions prepared with Kollidon VA 64 S. No.
SaturationSolubility is the extreme amount of a solute that dissolved in a specified solvent; such solution were prepared by adding extra quantities of FNS in distilled water and chloroform and shacked by shaker water bath for 10 min at 30°C. Filtration of solution was performed to exclude any unsolvable particles that might disturb the results. The results of saturationsolubility study are shown in Table 3.
ABSTRACT: Hydrochlorothiazide (HCT) is a class IV drug which has limited solubility and permeability, for overcome this problems co-crystallization method is used. Co-crystallization is the process to enhance the physical properties of drug molecule especially the solubility. HCT belongs to diuretic category and Atenolol (ATL) belongs to Beta blocker category they are combined for use in tablet formulation. Co-crystallization was used to combine two drugs in single solid phase and thus to achieve new approach for combination therapy to treat hypertension. Using the new approach co-crystals of ATL with HCT was prepared. Co-crystallization of two drugs were carried out by using solvent evaporation and solution co-crystallization method. The saturationsolubility was done to evaluate the solubility of co-crystals. Comparative drug release study was carried out between co-crystals and marketed formulation. The prepared co- crystals have shown several times faster release than marketed tablet and co-crystals were characterized by using DSC, FTIR and SEM. INTRODUCTION: Hydrochlorothiazide (HCT) is