Solubility Enhancement Techniques

This paper evaluated the performance of an envelope enhancement (EE) algorithm subjectively by children with auditory processing disorder (APD), and objectively through computational models. Speech intelligibility data was collected from children with APD, for unprocessed and envelope- enhanced speech in the presence of stationary and non-stationary background noise at different signal to noise ratios (SNRs), both with and without noise reduction (NR) algorithms as a front-end to the EE algorithm. Furthermore, intrusive and non-intrusive objective speech intelligibility metrics were derived to predict the perceptual impact of this EE algorithm. Subjective data for stationary noise conditions revealed that the combination of NR and EE algorithms significantly improved the speech intelligibility scores at poor SNRs. In contrast, the same combination was ineffective in improving speech intelligibility in non-stationary noise conditions. Taken together, subjective results suggest that exaggerating the envelope cues improves speech identification scores for children with APD. However, the benefit obtained varies depending upon the type and level of the background noise. Both intrusive and non-intrusive objective speech intelligibility estimators exhibited good correlation with the subjective data, with the intrusive metric demonstrating better generalization capabilities. Implications of these results for hearing aid applications for children with APD is discussed.

The solubility enhancement process of hydrophobic drugs is crucial in formulation development to achieve the bioavailability and therapeutic action of the drug at the target site. About 40% of the new chemical entities that have been identified by pharmaceutical industry screening programs face numerous problems in the formulation and development stage due to the poor water solubility and low bioavailability. Drug solubility and bioavailability enhancement are the important challenges in the field of formulation of pharmaceuticals. The Bio pharmaceutics Classification System depicts that Class II and IV drugs have a low water solubility, poor dissolution, and low bioavailability. This review highlights on the importance, advantages, disadvantages, techniques of solubility enhancement.

Introduction: Amorphous solid dispersions are considered as one of the most powerful strategies to formulate poorly soluble drugs. They are made up of an active pharmaceutical ingredient (API) dispersed at the molecular level in an amorphous polymeric carrier. As the latter component constitutes the largest part of the formulation, its characteristics will contribute to a large extent to the properties and behavior of the solid dispersion.

Areas covered: Amorphous polymers are most often used in modern solid dispersion formulations. This review discusses carrier properties like molecular weight, conformation, hygroscopicity, their stabilization effects, issues related to solid dispersion manufacturing technology, response to downstream processing, and potential to generate supersaturation, next to criteria to select a carrier to formulate stable amorphous solid dispersions.

Expert opinion: Different amorphous carriers lead to solid dispersions with various properties in terms of physical stability, phase behavior and drug release rate and extent. Despite more than 50 years of intensive research in this field it remains difficult to predict what carrier is best suited for a given API, pointing to the complex nature of this formulation strategy. Sustained efforts to understand the link and complex interplay between material properties, processing parameters, physical stability and dissolution behavior are required from pharmaceutical scientists with a strong physicochemical background to shift the development from trial and error to science driven.

Context: Drug solubility is one of the most important physicochemical properties for the development of new pharmaceutical products, which, in our study, is a new synthetic molecule, which has been shown to have a potential neuroprotective effect in rat.

Aims: To evaluate the equilibrium solubility of JM-20 within the physiological pH range and aqueous chemical stability.

Methods: It was performed at pH 1.2, 4.5 and 6.8 at 37 ± 0.5°C for 27 h by the method of the saturated flasks. HPLC and FTIR were used for the study of aqueous stability and to evaluate the molecular structure of the non-ionized fraction by DSC/TGA.

Results: Concentrations calculated at pH 1.2 were higher than at pH 4.5 and pH 6.8. A retention time greater than pH 4.5 and 6.8 after 24 h was detected in the aqueous stability study at pH 1.2, in addition to other peaks in these chromatograms. Analyses by FT-IR and DSC/TGA demonstrated the absence of polymorphism in the dissociated fraction of saturated solutions.

Conclusions: The JM-20 presented at 6 hours its maximum steady state of solubility, being inferior to pH 4.5 and 6.8. It is corroborated by the qualitative analysis by HPLC, that the compound is chemically unstable from 24 h to pH 4.5 and 6.8. By FT-IR and DSC/TG it was elucidated that the fractions of the molecule not dissociated, did not undergo structural changes in it, and it is inferred that there is no polymorphism.

Vapor pressure of aqueous methyldiethanolamine (MDEA) mixed with various concentrations of 1-butyl-3-methyl-imidazolium tetrafluoroborate ([bmim][BF4]) and 1-butyl-3-methyl-imidazoliumdicyanamide ([bmim][DCA]) have been measured and compared with conventional solvents. A standard response surface methodology (RSM) design, namely central composite design (CCD) has been applied in this work to investigate the effects of temperature and concentration of Piperazine, [bmim][BF4] and [bmim][DCA] on the vapor pressure of aqueous 4 kmol m−3 MDEA. The vapor pressure data of aqueous 4 kmol m−3 MDEA mixed with ionic liquids ranging from 0 to 2.0 kmol m−3 and temperatures ranging from 30 to 80 °C, showed that the ionic liquids reduced the vapor pressure of solvents with the order of [bmim][DCA] > [bmim][BF4]. The experimental values are in good agreement with the values predicted by the models. The model results showed that the quadratic model was suitable and sufficient for predicting the v...

Curcumin (CUR) is highly lipophilic drug that shows degradation at alkaline pH which restricts its oral
bioavailability. The aim of the present study was to enhance the oral bioavailability of CUR by increasing
its solubility and dissolution rate. Solid dispersions (SDs) of CUR in aqueous and organic solvent using
Eudragit EPO (EuD) were prepared by spray drying and rota evaporation technique. The solubility of plain
CUR in acidic pH 1.2 is only 0.02% whereas SDs containing EuD have solubilities of 40.29% and 18.78% by
spray drying and rota evaporation technique respectively. Physical characterization by SEM, IR, DSC, and
XRD studies, revealed the changes in solid state during the formation of dispersion and justified the
decreased crystallinity of CUR SDs. Dissolution studies showed that pH values influenced the release
profile lower the pH values higher the release speed (pH 1.2). CUR in pH 1.2 showed negligible release
even after 120 min (2e5%) whereas, SDs showed 20e45% drug release after 60 min. Further, insilico
docking study was carried out followed by molecular dynamic simulations to understand the molecular
level binding interactions between drug and polymer. The insilico studies demonstrates the role of van
der Waals interactions in binding of CUR to EuD.

A Liquisolid system is the one of the novel technique to enhance solubility and dissolution rate of poorly water soluble drug such as Itraconazole. In this technique liquisolid system refers to formulation of formed by water insoluble drug mix with non-volatile solvent which is further converted into free flowing, non adherent powder form and which is directly compressed into tablets. In that the polyethylene glycol 400 is used as non-volatile solvent in which drug having high solubility, Avicel PH 102 and Aerosil (silica) acts as carrier and coating material in the ratio of 5:1,10:1,15:1 and 20:1 respectively. Sodium starch glycolate acts as disintegrants and magnesium stearate as glidant in liquisolid system. The prepared liquisolid system were evaluated to their flowing properties such as bulk density, tap density, Hausner's ratio, Carr's index, and angle of repose. Differential scanning calorimetry(DSC),Fourier Transform Infrared spectroscopy (FTIR) , X Ray Diffraction (XRD) study ,Scanning electron microscope study show no interaction between the drug and excipients. Further tablets were evaluated hardness, diameter, thickness, weight variation, friability, disintegration test, uniformity of contents and in-vitro release study. the result show liquisolid compact of optimized batch F16 have 95.17 % in 60 min. which is higher percentage of drug release than conventional and marketed tablets because of due to increase in wetting properties and surface availability for dissolution.

Introduction: As a consequence of the target and drug candidate identification process, drugs with higher hydrophobicity and/or lipophilicity are being selected for further development, leading to solubility and dissolution rate limited oral bioavailability, and hence potential failure of the intended therapeutic goal. Solid dispersions were introduced as a formulation strategy in the early 1960s to tackle this issue and are still an area of intensive research activity.

Areas covered: There has been a shift in the type of carriers that were used in the formulation of solid dispersions as nowadays, amorphous carriers are most often used, whereas in early stages of solid dispersions development, crystalline and semi-crystalline carriers were most commonly applied. In this review, we will discuss several aspects related to the use of crystalline and semi-crystalline carriers such as their molecular and related physical structure, and their physical chemical properties related to formulation of poorly soluble drugs.

Expert opinion: The inherent crystallinity of this type of carrier hinders the formation of high-load solid solutions as mainly the amorphous domains of a carrier are able to accommodate drug molecules. Hence these carriers are not currently first choice excipients to formulate solid dispersions.

A strategy for adaptive control and energetic optimization of aerobic fermentors was implemented, with both air flow and agitation speed as manipulated variables. This strategy is separable in its components: control, optimization, estimation. We optimized parameter’s estimation (from the usual KLa correlation) using sinusoidal excitation of air flow and agitation speed. We have implemented parameter’s estimation trough recursive least squares algorithm with forgetting factor. We carried separate essays on control, optimization and estimation algorithms. We carried our essays using an original computational simulation environment, with noise and delay generating facilities for data sampling and filtering.

Our results show the convergence and robustness of the estimation algorithm used, improved with use of both forgetting factor and KLa dead-band facilities. Control algorithm used in our work compares favorably with PID using the integrated area criteria for deviation between oxygen molarity and critical molarity (set point). Optimization algorithm clearly reduces energetic consumption, respecting critical molarity. Integration of control, optimization and adaptive algorithms was implemented, but future work is needed for stability. Methods were defined and implemented for stability improvement. We have implemented data acquisition and computer manipulation of air flow and agitation speed for actual fermentors.

The present study was aimed to improve the water
solubility and bioavailability of telmisartan by solid dispersion technique.
Telmisartan is 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-
yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Telmisartan is practically
insoluble in water. Telmisartan is an angiotensin II receptor antagonist
(ARB), used in the management of hypertension. Solid dispersions of
telmisartan were prepared by using poly ethylene glycol 4000 and
mannitol as hydrophilic carriers in different weight ratios by solvent
evaporation method. The drug and the solid dispersions were
characterized by saturation solubility studies, in-vitro dissolution study,
Fourier-transform infrared spectroscopy, differential scanning
calorimetry, drug content estimation and stability study. Based on
physical characters and drug release pattern, formulation F2 (1 g drug, 4 g
PEG 4000 and 1 g mannitol) exhibited the best results. The carriers, poly
ethylene glycol 4000 and mannitol were found to be effective in
increasing the aqueous solubility and dissolution rate of telmisartan in
solid dispersions when compared to the pure drug.

tThe need for development of better surface active agents for upstream oil and gas industry whichcan survive harsh condition of salinity are in great demand, particularly for the applications related toimproved/enhanced oil recovery, flow assurance and oil and gas production operations keeping in mindthe environmental constraints. The technical difficulties which need to be considered are those involvingthe surface forces such as surface tension (SFT) and interfacial tension (IFT) acting between the formationwater and the low waxy crude oil. In this study, we have employed the use of eight aliphatic ionic liquids(ILs), based on di- and tri-alkyl ammonium as cations and with various anions such as [CH3COO]−, [BF4]−,[H2PO4]−and [HSO4]−for the investigation of the surface phenomenon of crude oil–water system. Thesynergistic effect of NaCl along with the ILs is investigated in detail. It is observed that there is a signifi-cant reduction in the surface tension of water and the interfacial tension of crude oil–water system in thepresence of salt, particularly at higher concentration of NaCl (200,000 ppm). Effect of temperature, time,alkyl chain length of the cationic part of the ILs, nature of anions of ILs and the concentration of ILs is alsodiscussed. The trend in the electrical conductivity of aqueous IL solutions with various concentrationsat three different temperatures 298.15–318.15 K is also presented along with critical aggregation con-centration. The study on the effect of ILs on the SFT/IFT of water and low waxy crude oil–water systemreveal that the ILs are successful in minimizing the effect of the surface forces in the presence of salt andthereby, could pave the way for efficient enhanced oil recovery operations.

Ionic liquids are ideal absorbents for vapour absorption refrigeration systems because of their low
volatility, and good solubility with different natural refrigerants such as ammonia, water, carbon dioxide,
etc. However, the high circulation ratio and viscosity of ionic liquids pose many problems such as high
pumping power and low absorber efficiency. One possibility is to use water as a cosolvent to overcome
these drawbacks. The results of our study on the performance of a vapour absorption refrigerator
operating with ammonia as the refrigerant and different ionic liquids and water as solvent and cosolvent
respectively are presented in this paper. The results show that the use of water as a co-solvent
results in a large decrease in circulation ratio, and hence the size of equipment, while the coefficient
of performance decreases slightly.

In this study, the physical solubility and diffusivity of N2O in aqueous MDEA+[bmim][BF4] solutions were measured over a range of temperatures of 303–333K and [bmim][BF4] concentrations of 0–2.0molL−1 at atmospheric pressure. The total MDEA concentration in the solutions was kept constant at 4molL−1. The “N2O analogy” was then used to estimate the physical solubility and diffusivity of CO2 in aqueous MDEA+[bmim][BF4] solutions. The density and viscosity of aqueous MDEA+[bmim][BF4] solutions were also measured over the same range of temperatures and concentrations of the ionic liquid. These data were used to develop correlations for the prediction of CO2 diffusivity in these systems.

In this study, the physical solubility and diffusivity of N 2O in aqueous MDEA+[bmim][BF 4] solutions were measured over a range of temperatures of 303-333K and [bmim][BF 4] concentrations of 0-2.0molL -1 at atmospheric pressure. The total MDEA concentration in the solutions was kept constant at 4molL -1. The " N 2O analogy" was then used to estimate the physical solubility and diffusivity of CO 2 in aqueous MDEA+[bmim][BF 4] solutions. The density and viscosity of aqueous MDEA+[bmim][BF 4] solutions were also measured over the same range of temperatures and concentrations of the ionic liquid. These data were used to develop correlations for the prediction of CO 2 diffusivity in these systems. © 2011.

http://ac.els-cdn.com/S1385894711007728/1-s2.0-S1385894711007728-main.pdf?_tid=660aa6dc-0ca1-11e4-95ee-00000aacb35f&acdnat=1405484987_8fb526066122f8d9fce5bd23f027b1da 
http://www.sciencedirect.com/science/article/pii/S1385894711007728

Liquisolid compact technique is a novel concept for delivery of drug through oral route. This
approach of delivering drug is mostly suitable for lipophilic drug and poorly or water insoluble drugs. The
main objective of present study was to increase the solubility of water in soluble BSc class II drug etoricoxib.
Etoricoxib is alipophilic drug that is practically insoluble in water and exhibit an excessively slow dissolution
rate in class II compound in biopharmaceutics classification system. The liquid solid compacts were prepared
using PEG 400 as non volatile solvent, microcrystalline cellulose as carrier, aerosil 200 as coating material
and Sodium starch glycolate was used as super disintegrating agent. Several formulations of liquid solid
compacts having different drug concentration in PEG 400 (non volatile solvent) with varying ratio of career
to coating material were prepared. The liquid solid compacts were evaluated for Bulk characterization, Flow
properties, solubility studies, drug content, FTIR studies, DSC studies and in vitro drug release studies. The
saturated solubility studies and in vitro drug release studies shows that the increase in solubility of drug and
enhanced drug release rate in liquisolid compacts compared to pure drug. The Formulation F5 andF4 is
considered as best formulation as it has shown highest drug release in short time (1 hr). Our studies showed
that the solubility of the drug can be significantly enhanced with increase in the carrier content there is
increase in the solubility resulting and enhanced drug release rate.

New protocol for screening efficient and environmentally friendly solvents was proposed and experimentally verified. The guidance for solvent selection comes from computed solubility via COSMO-RS approach. Furthermore, solute-solvent affinities computed using advanced quantum chemistry level were used as a rationale for observed solvents ranking. The screening protocol pointed out that 4-formylomorpholine (4FM) is an attractive solubilizer compared to commonly used aprotic solvents such as DMSO and DMF. This was tested experimentally by measuring the solubility of the title compounds in aqueous binary mixtures in the temperature range between 298.15 K and 313.15 K. Additional measurements were also performed for aqueous binary mixtures of DMSO and DMF. It has been found that the solubility of studied aromatic amides is very high and quite similar in all three aprotic solvents. For most aqueous binary mixtures, a significant decrease in solubility with a decrease in the organic fraction is observed, indicating that all systems can be regarded as efficient solvent-anti-solvent pairs. In the case of salicylamide dissolved in aqueous-4FM binary mixtures, a strong synergistic effect has been found leading to the highest solubility for 0.6 mole fraction of 4-FM.

The microstructure of pharmaceutical semi-crystalline solid dispersions has attracted extensive attention due to its complexity that might result in the diversity in physical stability, dissolution behavior, and pharmaceutical performance of the systems. Numerous factors have been reported that dictate the microstructure of semicrystalline dispersions. Nevertheless, the importance of the complicated conformation of the polymer has never been elucidated. In this study, we investigate the microstructure of dispersions of polyethylene glycol and active pharmaceutical ingredients by small-angle X-ray scattering and high performance differential scanning calorimetry. Polyethylene glycol with molecular weight of 2000 g/mol (PEG2000) and 6000 g/mol (PEG6000) exhibited remarkable discrepancy in the lamellar periodicity in dispersions with APIs which was attributed to the differences in their folding behavior. The long period of PEG2000 always decreased upon aging-induced exclusion of APIs from the interlamellar region of extended chain crystals whereas the periodicity of PEG6000 may decrease or increase during storage as a consequence of the competition between the drug segregation and the lamellar thickening from nonintegral-folded into integral-folded chain crystals. These processes were in turn significantly influenced by the crystallization tendency of the pharmaceutical compounds, drug−polymer interactions, as well as the dispersion composition and crystallization temperature. This study highlights the significance of the polymer conformation on the microstructure of semicrystalline systems that is critical for the preparation of solid dispersions with consistent and reproducible quality.

PREPARATION AND CHARECTERIZATION OF ZOTEPINE SOLID DISPERSIONS  BY CYCLODEXTRIN COMPLEXATION
Carmen Popescu1, Prashanth Manda2, Abhishek Juluri2, Leon Zhou1, Michael A. Repka2, S.Narasimha Murthy2.
1Roquette America, Inc, 2211Innovation Dr, Geneva IL, 60134.
2The University of Mississippi School of Pharmacy, University, MS, 38677.
Purpose
Zotepine is a potent atypical antipsychotic drug. Following oral administration, the systemic bioavailability is highly limited owing to its poor aqueous solubility. This project was focusing on Zotepine solubilization by cyclodextrin (CD) complexation using different solid dispersion methods and compares their efficiency.
METHODS
Cyclodextrin Complexation
-cyclodextrin (Kleptose®, CD) and three derivatives, two hydroxypropyl--cyclodextrins (Kleptose® HPB, HPBCD, molar degree of substitution 0.62 and Kleptose® HP, HPCD, MS=0.87) and a methylated--cyclodextrin (Crysmeb, MCD, MS=0.57) were used to complex Zotepine. Solid dispersions were obtained by complexation methods like physical blend (PM), spray drying (SD) and lyophilization (LYO). Based on previous phase solubility evaluation, Zotepine displayed an AL solubilization profile and was complexed at a 1:1 molar ratio.
Characterization by DSC and NMR
Solid dispersions were characterized by DSC (Perkin-Elmer Diamond) for Zotepine: CDs complex formation. NMR spectral data of the API, cyclodextrin and the Zotepine: CDs complex were done in order to check the possible chemical shifts between the drug and cyclodextrin during the process of complexation.
Dissolution Studies
The release kinetics of Zotepine from solid dispersion powders was evaluated by dissolution profile evaluation in artificial saliva as a dissolution medium at 370C and 75 rpm using USP type II apparatus.
RESULTS
Zotepine exhibited a melting endothermic peak around 93°C in the DSC thermogram. The solid dispersions prepared using PM and LYO are revealing higher drug peak intensity when compared to that of the solid dispersions prepared by SD indicating the possibility of reduced crystallinity of the drug (which might be due to of the drug internalization in the cyclodextrin cavity during complexation). The NMR spectral data illustrate a shift in the drug peak which infers an interaction between the drug and cyclodextrin due to the drug cyclodextrin complexation. The spray dried inclusion complexes obtained using HPBCD showed a Zotepine release of ~ 96% whereas in case of Crysmeb, complexes obtained by lyophilization showed a better dissolution profile (~93%) compared to that of the others methods.
Conclusion
Zotepine:HPBCD solid dispersion prepared by spray drying can make this API a very good  candidate for tablet formulation with  improved drug solubility and dissolution profile. The data obtained following DSC and NMR studies clearly demonstrate the amorphous nature and complexation of the drug with cyclodextrin.

Context: Pharmacological properties and studies of methods of extraction of mangiferin have been reported, but there are not studies related to the solubility of mangiferin in the solvents used in the pharmaceutical industry.

Aims: Study the solubility of mangiferin in different solvents used in the pharmaceutical industry.

Methods: The mangiferin used had a purity of 97.3% determined by High-Performance Liquid Chromatographic (HPLC), and solubility measurements were made in ethanol, methanol, water, acetone, diethyl ether, and hexane at 5, 15, 30, 40, 50 and 600C of temperature. The mangiferin concentrations were determined by ultraviolet spectrometry at 254 nm. The experimental solubility data were correlated with the Van´t Hoff equation and the dissolution heat determined.

Results: The solubility of mangiferin in pure solvents decreases with increasing of temperature and in the following order: ethanol>methanol>water>diethyl ether>acetone>n hexane.

Conclusions: This results indicated that mangiferin is slightly soluble in ethanol, sparingly soluble in methanol and water and practically insoluble in diethyl ether, acetone, and n-hexane.

Context: The use of quercetin as a potential active pharmaceutical ingredient is limited by low aqueous solubility leading to low bioavailability. A spray-dried solid dispersion technique is used to increase the solubility and dissolution profiles of quercetin.

Aims: To prepare and characterize quercetin solid dispersion using polyvinylpyrrolidone (PVP) K-30.

Methods: Solid dispersions (SDs) were prepared by spray drying technique at quercetin/PVP K-30 ratios of 10/90, 20/80, 30/70, 40/60 and 50/50. A physical mixture of quercetin/PVP K-30 (50/50) and pure quercetin were used as comparisons. The SDs were characterized by powder X-Ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform IR (FTIR) spectroscopy, solubility and dissolution studies. The effect of the drug/polymer ratio on the solubility of quercetin was also studied.

Results: Quercetin SDs appeared as amorphous form as confirmed by XRD. Quercetin was better dispersed as the drug/polymer ratio decreased. SD with ratio 10/90 showed regular spherical particles in the size range of 0-35 µm. The solubility of quercetin increased with decreasing drug/polymer ratio. Preparation of SDs influence the solubility significantly (p<0.01). The increase in solubility is probably due to a hydrogen bond between quercetin and PVP K30 as confirmed by FTIR spectra. SD with ratio 10/90 showed a high dissolution rate (95.12 ± 1.83%) within 120 min in comparison to pure quercetin (19.37 ± 0.58%) or physical mixture (37.85 ± 0.85%).

Conclusions: Preparation of quercetin SDs with PVP K30 by spray drying technique results in amorphous spherical particles. There was an increase in solubility and percent dissolved with a decrease in drug/polymer ratio.

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y 1), entrapment efficiency (Y 2) and drug release (Y 3). SLMs having a 10-40 µm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to-40 mV). The obtained outcomes for Y 1 (29-86 %), Y 2 (45-83 %) and Y 3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. N...

In this work, successful efforts have been performed for solubility enhancement of acyclovir. pH-sensitive b-Cyclodextrin-g-poly methacrylic acid (MAA) hydrogel microparticles were developed. b-Cyclodextrin, MAA, N,N-methylene bisacrylamide were used as polymer, monomer, and cross-linker, respectively. Nine different formulations (BM-1 to BM-9) were prepared by aqueous free radical polymerization. Developed microparticles were characterized for FTIR, Differential Scanning Calorimetry/Thermo Gravimetric Analysis, PXRD, energy-dispersive x-ray spectroscopy, SEM, TEM, optical microscopy, zeta sizer, percent equilibrium swelling (%ES), solubility studies, and in vitro drug release studies. Higher swelling results (83.68%) were obtained at pH 7.4 in less than 3 h. Porous surfaces with drug were seen in TEM images. Maximum release was observed at pH 7.4 (89.51%). Solubility enhancement was 7.38-fold in water as compared to pure acyclovir. Thermal stability of grafted microparti-cles was increased up to 440.13°C. A potential approach for solubility enhancement was successfully developed.

In the present study amount of Cefixime and amount of Metronidazole solubilised using PEG 6 K, PEG 20 K, PVP K 30, Brij 30 and Sodium lauryl sulphate alone and in combinations was investigated. Study results showed that drug amount solubilised by single surfactant was higher than water for both drugs and values were noticeable for Brij 30 and Sodium lauryl sulphate. Regarding drug amount solubilised using surfactant combination results showed synergistic effects and the effect was prominent when Brij 30 and Sodium lauryl sulphate were present in combination.

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y 1), entrapment efficiency (Y 2) and drug release (Y 3). SLMs having a 10-40 µm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to-40 mV). The obtained outcomes for Y 1 (29-86 %), Y 2 (45-83 %) and Y 3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Kors-meyer-Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

Introduction: Direct compression is the process of choice for tablet manufacturing due to its simplicity and lesser steps involved. For direct compression, the material of interest should have compressibility and compactibility. The aim of present work to convert valsartan drug powder into crystals those are directly compressible material. Materials and Methods: For the crystallo-co-agglomeration technique process, a system of Dimethylformamide-Water-Dichloromethane as good solvent-poor solvent-bridging liquid is used. Hydroxypropyl cellulose (HPC) was used to stabilize the system. Talc confirms its role as a bulking agent as well as the substrate for the spherical crystals. Results: The spherical crystals obtained in the presence of 0.5% HPC had greater particle size distribution, mechanical strength, compressibility, and compactibility in comparison to pure drug crystals. Drug content of the spherical crystals ranged around 84% and in vitro release for the optimized batch was 98.73%. In vivo bioavailability studies were performed in the Wistar rats, bioavailability (AUC) of the spherical crystals (18.90 ± 3.254 μg/ml*h) was significant (P < 0.05) to the pure drug (13.68 ± 0.902 μg/ml*h), and marketed preparation (17.49 ± 2.5 μg/ml*h). Stability studies in accordance to ICH guidelines indicated stability of the obtained products. Conclusion: Valsartan pure drug crystals were converted into the directly compressible material by crystallo-co-agglomeration technique. The obtained spherical crystals had greater solubility and flowability as compared to the original crystals.

In this study, the solubility of sodium chloride in 16 imidazolium-, pyrrolidinium-, pyridinium-, and ammonium-based ionic liquids at different temperatures was measured. The solubility of sodium chloride was found to increase with temperature in all of the ionic liquids studied. Both cations and anions in the ionic liquid affected solubility, but anions had more of an effect than cations. The highest measured solubility of sodium chloride was 8.96 wt % at 125 C in 1-ethyl-3-methylimidazolium dimethyl phosphate. The nonrandom two-liquid model was used to calculate the solubility of sodium chloride in some ionic liquids. The experimental and calculated values were in good agreement in many cases. © 2013 American Chemical Society.

http://pubs.acs.org/doi/pdfplus/10.1021/ie401282y

The primary aim of this review was to improve the solubility and Bioavailability of BCS Class-II drugs because of their low solubility and dissolution rate. Solubility is one of the imp parameter to achieve desired concentration of drug in systemic circulation for pharmacological response to be shown. Hence the classII drugs require enhancement in solubility and dissolution rate in there formulation development particularly in solid dosage form such as in tablet and capsule. So because of this there are several methods and newer emerging technologies have been developed for increasing the solubility as well as Bioavailability of class –II drugs. In this article review on literature on newer techniques or methods as well as recent research on formulation development of classII drugs was done.

A comprehensive experimental and theoretical screening was performed for identification of curcumin solubilizers. Experimental data led to formulation of a non-linear QSPR model correlating molecular descriptors with measured solubilities. The majority of synthesized binary systems exhibited a moderate enhancement of curcumin solubility, which was found to be the highest in the case of curcumin cocrystallized with pyrogallol. New excipients for curcumin were found by utilization of the model within its applicability domain. It appears that a five-fold rise of curcumin solubility is the upper limit for this kind of formulations what was inferred from the screened 230 thousand compounds. Finally, theoretical analysis was extended on naturally occurring curcumin analogues, including demethoxycurcumin, bisdemethoxycurcumin, α-, β- and Ar-turmerones. In all cases, a list of coformers suitable for binary solids preparation with potential enhanced solubility was obtained. They can be treated as first choice lists for further experimental exploration of solubility enhancement of curcumin and its analogues.