Equilibrium Solubility Studies Research Articles

Solid self-nanoemulsifying systems of olmesartan medoxomil: Formulation development, micromeritic characterization, in vitro and in vivo evaluation

The current studies entail development and evaluation of solid self-nanoemulsifying drug delivery systems (S-SNEDDS) employing porous carriers for enhancing the oral bioavailability of olmesartan medoxomil. Equilibrium solubility studies and pseudoternary phase diagrams revealed suitability of oleic acid, Tween 40 and Transcutol HP as the lipid, surfactant and cosolvent for formulation of the liquid SNEDDS (L-SNEDDS). The L-SNEDDS were systematically optimized using optimal mixture design, evaluated for emulsification time, globule size andin vitrodrug release. S-SNEDDS formulations were prepared by adsorbing L-SNEDDS onto the porous carriers,viz.Aerosil 200, Aeroperl 300, Sylysia 550, Neusilin US2 and Fujicalin SG, and evaluated for oil adsorption tendency, micrometric behavior, flow properties and compaction characteristics using Kawakita, Heckel and Leuenberger plots for identifying the suitable solid carrier for formulation of S-SNEDDS tablet.In vitrodissolution studies were performed for comparative analysis of the drug release behavior from the S-SNEDDS formulation. Among the various solid carriers employed, Neusilin US2 exhibited superior oil adsorbing capacity, micrometric properties, excellent flowability and compactibility. Nearly 2.6-fold improvement in the drug release rate was observed from the optimized S-SNEDDS, followed by no significant difference in the drug release rate as compared to the L-SNEDDS (p>0.05).In vivopharmacokinetic studies in Wistar rats revealed 2.32 and 3.27-fold enhancement in Cmaxand AUC of the drug from the optimized S-SNEDDSvis-à-visthe pure drug solution. Also, high degree of prognostic ability ofin vitrodissolution performance within vivoperformance was revealed from level Ain vitro/in vivocorrelations (IVIVC). In a nutshell, the present studies report successful development of S-SNEDDS of olmesartan medoxomil as one of the promising formulation strategies with distinctly improved biopharmaceutical attributes.

Stability-Indicating HPTLC Method for Quantitative Estimation of Asenapine Maleate in Pharmaceutical Formulations, Equilibrium Solubility, and ex vivo Diffusion Studies

New high-performance thin layer chromatography (HPTLC) has been successfully developed and validated for quantitative estimation of Asenapine maleate in both marketed tablets and in-house developed formulations (solution, microemulsion, nanoemulsion, and mucoadhesive nanoemulsion) as well as for equilibrium solubility study and ex vivo diffusion study of developed formulation through natural membrane. As suggested by the International Conference on Harmonization, different stress test conditions (alkali, acid, thermal, photolytic, and humidity) were used to degrade Asenapine maleate. The samples produced from this study were utilized to develop a stability indicating HPTLC method. The Asenapine maleate was separated well from degradation products using HPTLC plate; precoated with silica gel G 60 F254 on aluminum sheet as a stationary phase and methanol as a mobile phase. Using densitometric analysis, Asenapine maleate was quantified at 235 nm. The method produced compact band for the drug (Rf = 0.43 + 0.02). The HPTLC method was validated and statistical analysis of the data confirmed the method to be specific, linear, accurate, precise, reproducible, and selective for Asenapine maleate’s analysis. This method was successfully used for assay of Asenapine maleate in both marketed tablets and in-house developed formulations, determining equilibrium solubility in various excipients as well as its ex vivo diffusion study through sheep nasal mucosa from the formulations developed in-house.

QbD-Oriented Development of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) of Valsartan with Improved Biopharmaceutical Performance.

The objectives of the present studies were to develop the systematically optimized selfnanoemulsifying drug delivery systems (SNEDDS) of valsartan employing the holistic QbD approach. The quality profile target product (QTPP) was defined and critical quality attributes (CQAs) earmarked. Preformulation studies including the equilibrium solubility and pseudoternary phase titration studies facilitated the selection of suitable lipids and emulgents for formulation of SNEDDS. Risk assessment and factor screening studies facilitated the selection of Lauroglycol FCC and Capmul MCM L8 (i.e., lipid), Tween 40 and Tween 80 (i.e., emulgent) as the critical material attributes (CMAs) for SNEDDS prepared using medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs). A central composite design (CCD) was employed for systematic optimization of SNEDDS, taking globule size (Dnm), drug release in 10 min (Q10min) and amount permeated in 45 min (%Perm45min) as the CQAs. Design space was generated using apt mathematical models to embark upon the optimized formulations and validation of the QbD. In situ SPIP studies revealed significant improvement in the absorptivity and permeability parameters of SNEDDS owing to the inhibition of P-gp/MRP2 efflux vis-à-vis the conventional marketed formulation and pure drug. In vivo pharmacokinetic studies corroborated marked enhancement in the oral bioavailability drug from SNEDDS vis-à-vis the marketed formulation. Establishment of various levels of in vitro/in vivo correlations (IVIVC) indicated excellent goodness of fit between the in vitro drug release data with the in vivo absorption parameters. In a nutshell, the present studies report successful QbD-based development of MCT and LCT-SNEDDS of valsartan with improved biopharmaceutical performance.

Preparation and characterization of dipyridamole solid dispersions for stabilization of supersaturation: effect of precipitation inhibitors type and molecular weight

Dipyridamole (DPL) is a weakly basic BCS class II drug which precipitates upon entering into intestine leading to pH dependant and variable absorption. Thus, research envisaged focuses on developing formulations that maintain supersaturation following upon acid to neutral pH transition. In an endeavor to accomplish the objective, solid dispersion (SD) with hydroxypropylmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) was prepared by a quench cooling method. The three molecular weight grades of HPMC (HPMC E5, HPMC E15 and HPMC E50) and two molecular weight grades of PVP (PVP K30 and PVP K90) were investigated to observe effect of increasing molecular weight on stabilizing DPL supersaturated solutions. Equilibrium solubility studies revealed increase in solubility with both HPMC and PVP with greater benefit from HPMC. In vitro supersaturated dissolution results demonstrated that HPMC formulations provided greater degree and extent of supersaturation as compared to PVP formulations. The formulation with HPMC E50 provided maximum stabilization to supersaturation upon acid to neutral pH transition. Moreover, the effect of increase in molecular weight was more pronounced in HPMC rather than PVP. Stronger interactions were observed for DPL with HPMC, while no interaction was observed with PVP which was evident from Fourier transform infra-red studies. Differential scanning calorimetry and powder X-ray diffraction studies revealed the amorphous state of DPL in SD.

Solubility in the reciprocal quaternary K+-Na+-SO42−-VO3−-H2O system at (293.15 and 313.15) K

The equilibrium solubility studies of the Na2SO4+KVO3+H2O system at 293.15 and 313.15K have been performed. Based on the results, the equilibrium plots for the system in a planar projection have been obtained according to the Jänecke method. The plots enable the determination of the optimal conditions for the conversion reaction of potassium metavanadate into complex salt sodium, potassium metavanadate with the use of sodium sulfate. The aim of the process is the recovery of vanadium compounds from solutions obtained after leaching spent vanadium catalyst.

Optimized self-nanoemulsifying drug delivery system of atazanavir with enhanced oral bioavailability: in vitro/in vivo characterization

Background: Atazanavir (ATV) is a HIV protease inhibitor. Due to its intense lipophilicity, the oral delivery of ATV encounters several problems such as poor aqueous solubility, pH-dependent dissolution and rapid first-pass metabolism in liver by CYP3A5, which result in low and erratic bioavailability.Objective: The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides of ATV in an attempt to circumvent such obstacles.Methods: Equilibrium solubility studies indicated the choice of Maisine 35-1 as lipid, and of Transcutol P and Span 20 as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X1) and surfactant (X2) as the critical factor variables. The SNEDDS were optimized (OPT) using 32 central composite design and the OPT formulation located using overlay plot. The pharmacokinetics and in situ single-pass intestinal perfusion studies of OPT formulation were investigated in Wistar rats.Results: OPT formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT formulation. Augmentation in the values of Ka (1.96-fold) and AUC (2.57-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug. Successful establishment of in vitro/in vivo correlation Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions.Conclusion: The studies, therefore, indicate the successful formulation development of SNEDDS with distinctly improved bioavailability of ATV.

Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies

Trans-resveratrol (t-RVT) is a potent antioxidant. By virtue of extensive pre-systemic metabolism and existence of enterohepatic recirculation, t-RVT bioavailability is almost zero. The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides (LCTs) of t-RVT in an attempt to circumvent such obstacles. Equilibrium solubility studies indicated the choice of Lauroglycol FCC as lipid, and of Labrasol and Transcutol P as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X1) and surfactant (X2) as the critical factor variables. The SNEDDS were optimized using 32 central composite design (CCD) and the optimized formulation (OPT) located using overlay plot. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the SNEDDS. Optimized formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT. Augmentation in the values of Ka (3.29-fold) and AUC (4.31-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT compared with pure drug. In situ perfusion (SPIP) studies in Wistar rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-à-vis the pure drug. Successful establishment of level A of in vitro/in vivo correlation substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The present study, therefore, reports the successful development of SNEDDS with distinctly enhanced bioavailability of t-RVT.

Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique

The present research was aimed at the enhancement of the dissolution rate of atorvastatin calcium by the solid dispersion technique using modified locust bean gum. Solid dispersions (SD) using modified locust bean gum were prepared by the modified solvent evaporation method. Other mixtures were also prepared by physical mixing, co-grinding, and the kneading method. The locust bean gum was subjected to heat for modification. The prepared solid dispersions and other mixtures were evaluated for equilibrium solubility studies, content uniformity, FTIR, DSC, XRD, in vitro drug release, and in vivo pharmacodynamic studies. The equilibrium solubility was enhanced in the solid dispersions (in a drug:polymer ratio of 1:6) and other mixtures such as the co-grinding mixture (CGM) and kneading mixture (KM). Maximum dissolution rate was observed in the solid dispersion batch SD3 (i.e. 50% within 15 min) with maximum drug release after 2 h (80%) out of all solid dispersions. The co-grinding mixture also exhibited a significant enhancement in the dissolution rate among the other mixtures. FTIR studies revealed the absence of drug-polymer interaction in the solid dispersions. Minor shifts in the endothermic peaks of the DSC thermograms of SD3 and CGM indicated slight changes in drug crystallinity. XRD studies further confirmed the results of DSC and FTIR. Topological changes were observed in SEM images of SD3 and CGM. In vivo pharmacodynamic studies indicated an improved efficacy of the optimized batch SD3 as compared to the pure drug at a dose of 3 mg/kg/day. Modified locust bean gum can be a promising carrier for solubility enhancement of poorly water-soluble drugs. The lower viscosity and wetting ability of MLBG, reduction in particle size, and decreased crystallinity of the drug are responsible for the dissolution enhancement of atorvastatin. The co-grinding mixture can be a good alternative to solid dispersions prepared by modified solvent evaporation due to its ease of preparation and significant improvement in dissolution characteristics.

In Vitro Dissolution Enhancement of Ondansetron by Solid Dispersion in Superdisintegrants

Ondansetron hydrochloride (OSH) is a highly selective and potent antagonist of 5-hydroxytryptamine at 5HT3 receptors in the gastrointestinal tract where it blocks both sites of serotonin induced nausea and vomiting. Physical mixtures and solid dispersions of the drug using superdisintegrants as carriers were prepared by a solvent method at different drug–carrier (w/w) ratios and evaluated with an objective of enhancing the dissolution rate of OSH from solid dispersion. Equilibrium solubility studies were performed for drug–carrier interactions in solution, and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC) studies were carried out to characterize the solid dispersions. FTIR spectra reveal no chemical interaction between the drug and superdisintegrants. XRD and DSC data indicate OSH was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. A marked enhancement in the dissolution of OSH was observed with all the superdisintegrants.

Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides

The objective of the current work is to develop systematically optimized self-nanoemulsifying drug delivery systems (SNEDDS) using long chain triglycerides (LCT's) and medium chain triglycerides (MCT's) of ezetimibe employing Formulation by Design (FbD), and evaluate their in vitro and in vivo performance. Equilibrium solubility studies indicated the choice of Maisine 35-1 and Capryol 90 as lipids, and of Labrasol and Tween 80 as emulgents for formulating the LCT and MCT systems, respectively. Ternary phase diagrams were constructed to select the areas of nanoemulsion, and the amounts of lipid (X1) and emulgent (X2) as the critical factor variables. The SNEDDS were systematically optimized using 32 central composite design and the optimized formulations located using overlay plot. TEM studies on reconstituted SNEDDS demonstrated uniform shape and size of globules. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the optimized SNEDDS. Thermodynamic studies, cloud point determination and accelerated stability studies ascertained the stability of optimized formulations. In situ perfusion (SPIP) studies in Sprague Dawley (SD) rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-à-vis the conventional marketed product. In vivo pharmacodynamic studies in SD rats indicated significantly superior modification in plasma lipid levels of optimized SNEDDS vis-à-vis marketed product, inclusion complex and pure drug. The studies, therefore, indicate the successful formulation development of self-nanoemulsifying systems with distinctly improved bioavailability potential of ezetimibe.

Dissolution enhancement of glimepiride using modified gum karaya as a carrier

Objective:The aim of present investigation is to enhance in vitro dissolution of poorly soluble drug glimepiride by preparing solid dispersions using modified gum karaya.Materials and Methods:Solid dispersions of drug were prepared by solvent evaporation method using modified gum karaya as carrier. Four batches of solid dispersion (SD1, SD4, SD9, and SD14) and physical mixture (PM1, PM4, PM9, and PM14) were prepared and characterized by differential scanning colorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, powder X-Ray diffraction (X-RD), and scanning electron microscopy (SEM) studies. Equilibrium solubility studies were carried out in shaker incubator for 24 h and in vitro drug release was determined using USP Dissolution Apparatus-II.Results:Maximum solubility and in vitro dissolution were observed with Batch SD4. No significant enhancement of dissolution characteristics were observed in the corresponding physical mixture PM4. Low viscosity with comparable swelling characteristics as compared to GK of modified form of gum karaya may lead to improvement in dissolution behavior of solid dispersion batches. Also, the conversion of crystalline form of drug to amorphous form may be a responsible factor, which was further confirmed by DSC, FTIR studies, and X-RD studies. SEM photographs of batch SD4 revealed porous nature of particle surface.Conclusion:Modified forms of natural carriers prove beneficial in dissolution enhancement of poorly soluble drugs and exhibited a great potential in novel drug delivery systems.

Solubility in the Reciprocal Quaternary NH4+–Na+–NO3––VO3––H2O System at (313 and 323) K

The equilibrium solubility studies of the NH4NO3 + NaVO3 + H2O system at (313 and 323) K have been performed. On the basis of the results, the equilibrium plots for the system in a planar projection have been obtained according to the Janecke method. The plots enable the determination of the optimal conditions for the conversion reaction of ammonium nitrate into sodium nitrate with the use of sodium metavanadate. The source of ammonium nitrate is the postfiltration lye from the soda production with the soda–chlorine–saltpeter (SCS) method. The conversion of NH4NO3 from the postfiltration lye into NaNO3 cancels the risk of explosion during the process of production of ammonium–sodium saltpeter.

HPTLC method development and validation: Quantification of paliperidone in formulations and in vitro release study

A new, economic, environmentally friendly and rapid high-performance thin-layer chromatographic (HPTLC) method was developed and validated for quantitative determination of paliperidone. The HPTLC separation was achieved on an aluminium-backed layer of silica gel 60F254 using methanol–ethyl acetate (8.0 + 2.0 v/v) as mobile phase. Quantitation was achieved by densitometric analysis at 284 nm over the concentration range of 100–600 ng mL−1. The method was found to give compact spot for the drug (Rf 0.54 ± 0.011). The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.9997. The method was validated for precision, recovery, repeatability, and robustness as per the International Conference on Harmonization guidelines. The minimum detectable amount was found to be 15.11 ng/spot, whereas the limit of quantitation was found to be 45.79 ng/spot. Statistical analysis of the data showed that the method is precise, accurate, reproducible, sensitive and selective for the analysis of paliperidone. The method was successfully employed for the estimation of paliperidone as a bulk drug, equilibrium solubility study, commercially available tablet formulation, mucoadhesive microemulsion formulations and solution (developed in-house).

Dihydroartemisinin-cyclodextrin complexation: Solubility and stability

Dihydroartemisinin (DHA) is a major metabolite of artemisinin and its derivatives, including arteether, artemether, and artesunate. To improve the solubility and stability of poorly soluble DHA, we prepared inclusion complexes with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and recrystalized DHA to study its thermal stability. The complexes were characterized by differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), thermal stability, phase, and equilibrium solubility studies. Pure DHA was crystalline and remained crystalline after recrystallization, but its unit cell dimensions changed as exhibited by XRD. DHA-HPbetaCD complexes showed a phase transitions towards amorphous in DSC thermograms, FTIR spectra, and XRD patterns. The phase solubility profiles of complexes prepared in water, acetate buffer, and phosphate buffers were classified as A(L)-type, indicating the formation of a 1:1 stoichiometric inclusion complex. The equilibrium solubility of DHA was enhanced as a function of HPbetaCD concentration. DHA-HPbetaCD complexes showed an 89-fold increase in solubility compared to DHA. Solubilities of complexes containing 275.1 mM HPbetaCD in water, acetate buffer (pH 3.0), and phosphate buffer (pH 3.0 and 7.4) were 10.04, 7.96, 6.30, and 11.61 mg/ml, respectively. Hydrogen bonding was found between DHA and HPbetaCD, and it was stronger in complexes prepared in water than in buffers. However, the AH values were higher in buffer than water. DHA-HPbetaCD complexes prepared using commercial (untreated) or recrystallized DHA (no detectable impurity) showed a 40% increase in thermal stability (50 degrees C) and a 29-fold decrease in hydrolysis rates compared with DHA. The rank order of stability constants (K(s)) was: water, acetate buffer (pH 3.0), phosphate buffer (pH 3.0), and phosphate buffer (pH 7.4). Thus, HPbetaCD complexation with recrystalized DHA increases DHA solubility and stability.

Characterization of a nematic mixture by reversed‐phase HPLC and UV spectroscopy: an application to phase behaviour studies in liquid crystal–CO2 systems

In the present work a simple but selective reversed‐phase high performance liquid chromatographic method (HPLC) was developed for the analysis of the nematic liquid crystal mixture E7 to determine precisely the composition of the liquid crystal mixture used in PDLC film preparation. Ultraviolet absorption spectrophotometry experiments were carried out to determine the HPLC detection wavelength and to characterize the absorptivity constants of E7 constituents. The technique developed is applied in the case of equilibrium solubility studies for E7 in supercritical carbon dioxide (scCO2). The results indicate unambiguously that scCO2 can fractionate the mixture towards the E7 components. The four single component peaks of the E7 mixture were distinctively separated by this method, which enabled the determination of the solubility of E7 constituents in the scCO2.

The role of β93 Cys in the inhibition of Hb S fiber formation

Recent studies have suggested that nitric oxide (NO) binding to hemoglobin (Hb) may lead to the inhibition of sickle cell fiber formation and the dissolution of sickle cell fibers. NO can react with Hb in at least 3 ways: 1) formation of Hb(II)NO, 2) formation of methemoglobin, and 3) formation of S-nitrosohemoglobin, through nitrosylation of the β93 Cys residue. In this study, the role of β93 Cys in the mechanism of sickle cell fiber inhibition is investigated through chemical modification with N-ethylmaleimide. UV resonance Raman, FT-IR and electrospray ionization mass spectroscopic methods in conjunction with equilibrium solubility and kinetic studies are used to characterize the effect of β93 Cys modification on Hb S fiber formation. Both FT-IR spectroscopy and electrospray mass spectrometry results demonstrate that modification can occur at both the β93 and α104 Cys residues under relatively mild reaction conditions. Equilibrium solubility measurements reveal that singly-modified Hb at the β93 position leads to increased amounts of fiber formation relative to unmodified or doubly-modified Hb S. Kinetic studies confirm that modification of only the β93 residue leads to a faster onset of polymerization. UV resonance Raman results indicate that modification of the α104 residue in addition to the β93 residue significantly perturbs the α 1β 2 interface, while modification of only β93 does not. These results in conjunction with the equilibrium solubility and kinetic measurements are suggestive that modification of the α104 Cys residue and not the β93 Cys residue leads to T-state destabilization and inhibition of fiber formation. These findings have implications for understanding the mechanism of NO binding to Hb and NO inhibition of Hb S fiber formation.

Permeability assessment of poorly water‐soluble compounds under solubilizing conditions: The reciprocal permeability approach

The objective of this study was to develop a general method to assess the intestinal permeability of poorly water‐soluble drugs where low‐aqueous drug solubility requires conduct of experiments under solubilizing experimental conditions. The permeability (Papp) of diazepam (DIA) was assessed across excised rat jejunum in the absence (Pappcontrol) and presence (Pappuncorr) of polysorbate‐80 (PS‐80). The micellar association constant (Ka) of DIA, estimated via equilibrium solubility studies, was used to correct Pappuncorr data and obtain an estimate of the true permeability coefficient (Pappcorr). An alternate approach was also developed (the reciprocal permeability approach) to allow direct estimation of Pappcorr without the need for independent estimation of Ka. The approach was further examined experimentally using a range of model drugs. DIA Pappcorr values obtained using the Ka from equilibrium solubility studies deviated from Pappcontrol values, especially at PS‐80 concentrations above 0.1% w/v. In contrast, data obtained using the reciprocal permeability method were consistent with Pappcontrol across the PS‐80 concentration range. Similar trends were observed with propranolol (PRO), antipyrine (ANT), naproxen (NAP), and cinnarizine (CIN). The reciprocal permeability approach therefore provides a simple and accurate method by which the permeability of poorly water‐soluble compounds may be estimated under solubilizing conditions.

Drug complexation and physicochemical properties of vinylpyrrolidone‐N,N′‐dimethylacrylamide copolymers

AbstractSolid dispersions of the nonsteriodal antiinflammatory drug (NSAID) 2′,4′‐difluoro‐4‐hydroxy‐(1,1′‐biphenyl)‐3‐carboxylic acid (DIF) with the water‐soluble random copolymer poly(N‐vinyl‐2‐pyrrolidone‐co‐N,N′‐dimethylacrylamide) (VP‐co‐DMAm) were prepared by the solvent method (coevaporates) and melting DIF/VP‐co‐DMAm (cofused) physical mixtures. Differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and X‐ray diffraction (XRD) were used to elucidate the possible interaction between the NSAID drug and VP‐co‐DMAm in cofused and coevaporated polymer–drug solid dispersions. The XRD and FTIR studies suggest the presence of physical interactions with formation of a charge transfer complex between DIF and the VP‐co‐DMAm copolymers as a consequence of the coevaporation or cofusion processes. In solution, dynamic and equilibrium solubility studies were determined to elucidate the mechanism of interaction between DIF and VP‐co‐DMAm copolymers. Thermodynamics data about the DIF: VP‐co‐DMAm dissolution process indicate that the coevaporated systems are more stable that the cofused systems. The dissolution of the cofused and coevaporated systems was diffusion controlled and the dissolution kinetics followed the Noyes–Whitney and the Levich equations. Molecular simulations using semiempirical quantum chemical calculations reinforce the experimental results, suggesting that the improvement in the DIF solubility could be attributed to the charge transfer complex formation between the drug and VP‐co‐DMAm copolymers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1337–1347, 2004

Nimesulide-Modified Gum Karaya Solid Mixtures: Preparation, Characterization, and Formulation Development

Solid mixtures of nimesulide (NS) and modified gum karaya (MGK) were prepared to improve the dissolution rate of NS. The effect of drug-carrier ratio on dissolution rate of NS was investigated by preparing the solid mixtures of different ratios by cogrinding method. Solid mixtures were also prepared by physical mixing, kneading, and solid dispersion techniques to study the influence of method of preparation. Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and equilibrium solubility studies were performed to explain the results of in vitro dissolution rate studies. It was clearly evident from the results that the NS dissolution rate was dependent on the concentration of MGK in the solid mixtures, and optimum weight ratio was found to be 1:4 (NS:MGK). Though the dissolution rate of NS from all solid mixtures prepared by different methods improved significantly, maximum improvement in dissolution rate was observed with solid dispersions. The order of methods basing on their effect on dissolution efficiency is solid dispersion>kneading>cogrinding> physical mixing>pure NS. Tablets of pure drug and solid mixtures (1:4 w/w, NS:MGK) were prepared. Though the best results from the dissolution test were obtained for the tablets containing solid dispersions, tablets containing cogrinding mixture were found to be suitable, from a practical point of view, for commercialization.

Nonideal equilibrium dissolution of trichloroethene from a decane‐based nonaqueous phase liquid mixture: Experimental and modeling investigation

Batch equilibrium solubility studies were conducted to examine the solubilization behavior of a chlorinated solvent, trichloroethene (TCE), from a fuel‐based nonaqueous phase liquid (NAPL) mixture. An alkane (n–decane) was used as a model compound because it is often a primary compound in jet fuel. The NAPL phase mole fractions of the chlorinated solvent in the mixture (XTCEN) that were investigated are typical of in situ values found at industrial and military waste sites (0.0001 ≥ XTCEN ≤ 0.1). The measured aqueous concentrations of TCE were essentially equal to the concentrations predicted with ideal dissolution theory (Raoult's law) at XTCEN values near 0.1. However, the ratio of the measured concentration to the ideal concentration, or the NAPL phase activity coefficient (γNTCE), increased nonlinearly as the XTCEN decreased. The γTCEN approached 6 at XTCEN = 0.0001. The UNIFAC method greatly underpredicts the γTCEN in this surrogate fuel. A NAPL‐mixture equilibrium‐dissolution model was developed that incorporates the observed nonideal dissolution. This model indicates that nonideal NAPL dissolution is 4 times faster than ideal dissolution for a hypothetical NAPL mixture with an initial XTCEN = 0.001. The magnitude of this effect becomes more important as the initial value of the XTCEN is decreased.