Rutesh Dave - Academia.edu (original) (raw)

Papers by Rutesh Dave

AAPS PharmSciTech, 2016

Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion metho... more Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion method and characterize them for their physicochemical and performance properties. Binary mixtures of ibuprofen and poloxamer were prepared in three different ratios (1:0.25, 1:0.5, and 1:0.75, respectively) using a water-jacketed high shear mixer. In vitro dissolution and saturation solubility studies were carried out for the drug, physical mixtures, and formulations for all ratios in de-ionized water, 0.1 N HCl (pH = 1.2), and phosphate buffer (pH = 7.2). Thermal and physical characterization of samples was done using modulated differential scanning calorimetry (mDSC), X-ray powder diffraction (XRD), and infrared spectroscopy (FTIR). Flow properties were evaluated using a powder rheometer. Maximum solubility enhancement was seen in acidic media for fused formulations where the ratio 1:0.75 had 18-fold increase. In vitro dissolution studies showed dissolution rate enhancement for physical mixtures and the formulations in all three media. The most pronounced effect was seen for formulation (1:0.75) in acidic media where the cumulative drug release was 58.27% while for drug, it was 3.67%. Model independent statistical methods and ANOVA based methods were used to check the significance of difference in the dissolution profiles. Thermograms from mDSC showed a characteristic peak for all formulations with T peak of around 45°C which suggested formation of a eutectic mixture. XRD data displayed that crystalline nature of ibuprofen was intact in the formulations. This work shows the effect of eutectic formation and micellar solubilization between ibuprofen and poloxamer at the given ratios on its solubility and dissolution rate enhancement.

Nanocrystals have emerged as a potential formulation strategy to eliminate the bioavailability-re... more Nanocrystals have emerged as a potential formulation strategy to eliminate the bioavailability-related problems by enhancing
the initial dissolution rate and moderately super-saturating the thermodynamic solubility. This review contains an in-depth knowledge of,
the processing method for formulation, an accurate quantitative assessment of the solubility and dissolution rates and their correlation to
observe pharmacokinetic data. Poor aqueous solubility is considered the major hurdle in the development of pharmaceutical compounds.
Because of a lack of understanding with regard to the change in the thermodynamic and kinetic properties (i.e., solubility and dissolution
rate) upon nanosizing, we critically reviewed the literatures for solubility determination to understand the significance and accuracy of the
implemented analytical method. In the latter part, we reviewed reports that have quantitatively studied the effect of the particle size and
the surface area change on the initial dissolution rate enhancement using alternative approaches besides the sink condition dissolution.
The lack of an apparent relationship between the dissolution rate enhancement and the observed bioavailability are discussed by reviewing
the reported in vivo data on animal models along with the particle size and food effect. The review will provide comprehensive information
to the pharmaceutical scientist in the area of nanoparticulate drug delivery.

International Journal of Pharmaceutical Sciences and Research

Solvent used for preparing binder solution in wet granulation process is one of the major factors... more Solvent used for preparing binder solution in wet granulation process is one of the major factors which dictate the granule properties. Aim of our current research was to understand the effect of solvents on flow properties of Microcrystalline Cellulose granules prepared using Hydroxypropyl Methylcellulose as binder by using rheological tools and subsequently studying the effect of relative humidity on rheology of dried granules. Granules were prepared by using 2.5 %w/w binder solution in water and water: ethanol mixture (20:80v/v). Prepared granules were dried, sieved and further analyzed. Effect of relative humidity on flowability of dried granules were studied at 22%, 52%, 75% RH at room temperature for 48 hours. Modulated Differential Scanning Calorimetry and Powder rheometer was used to study the thermal and flow properties of wet, dried and humidity exposed granules. Results show that the hydro - alcoholic batches show greater resistance to flow in wet granule sta ge. But, its...

Journal of pharmaceutical sciences, Jan 26, 2015

The quantitative determination of solubility and the initial dissolution rate enhancement of crys... more The quantitative determination of solubility and the initial dissolution rate enhancement of crystalline nanoparticles were critically investigated using a separation-based approach (ultracentrifugation and filtration). Four poorly soluble model compounds (griseofulvin, celecoxib, compound-X, and fenofibrate) were used in this investigation. The effect of the stabilizer concentration on the solubility of the unmilled compound was determined first to quantify its impact on the solubility and used for comparing solubility enhancement upon nanosizing. Methodologies were established for ultracentrifugation, ensuring satisfactory separation of crystalline nanoparticles. The data obtained using separation-based methodologies proved to be accurate, reproducible, and were in fair agreement with what would be predicted from the Ostwald-Freundlich equation. The dissolution studies under sink conditions were proved to be less efficient in quantifying the initial dissolution rate of crystalline...

The objective of this research was to develop and evaluate physicochemical properties of acetamin... more The objective of this research was to develop and evaluate physicochemical properties of acetaminophen and aspirin orally disintegrating strips with high loading dose. The strips were compared with conventional over the counter strips and chewable tablets for their mechanical and chemical properties. Aspirin (81 mg) and acetaminophen (80 mg) oral dissolving films were developed with 50-55% of drug loading and were compared with GAS-X ® (62.5 mg) and chewable tablets (aspirin and acetaminophen). Orally dissolving films were developed using a solvent casting method. Sonication was proven to be a more competent step in order to load a high amount of active drug substance in the thin film strips. Different film formulations were prepared by varying concentration of polymers and plasticizers. Optimization of formulation was done by conducting studies for various mechanical properties using TA-XT plus texture analyzer. Dissolution of optimized formulation was performed in 250 ml of pH 1.2 and artificial saliva (pH 6.8). The study was conducted by stirring the dissolution media at 50 rpm, 37 C for 30 minutes and was analyzed using UV/Vis spectroscopy. The dimensions of orally dissolving films were determined with the help of vernier calipers. Modulated Differential Scanning Calorimetry (MDSC) was also performed for the filmstrips to check the compatibility. The film strip was evaluated for imperfections and cuts, peelability without rupturing, folding and cracking endurance, surface roughness, tensile strength, film burst and disintegration time with the help of TA-XT plus texture analyzer. Moisture content was performed, on the fresh, as well as stability samples. Dissolution of filmstrips showed much faster release as compared to respective chewable tablets in artificial saliva as well as in pH 1.2. Disintegration times for filmstrips were also comparable to Gas-X ® and Listerine ® . After one month stability of filmstrips at room temperature, dissolution profiles perceived with negligible change. Other mechanical properties of the filmstrips were also comparable to Gas-X ® . DSC results suggest miscibility in polymer, which explains the increase in dissolution rate of filmstrips at high dose loading. Hence, in conclusion we develop a new in house method to formulate a stable and more efficient formulation for high loading dose of aspirin and acetaminophen.

Journal of Pharmaceutical Sciences, 2011

Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic d... more Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic drugs by extending their transit time is a promising approach. Swellable systems were evaluated for this purpose. Such systems demonstrate dual mechanism of release-diffusion and erosion. GRDDS requires maintaining its dimensions, which demands diffusion as a predominant mechanism of release (Fickian). In this work, dypyridamole, a weakly basic drug, together with various grades of hydroxypropyl methylcellulose and different excipients were evaluated for release and swelling properties. Dissolution data were analyzed by curve fitting to various models to estimate predominant release mechanism. It was found that matrices containing a swellable diluent like microcrystalline cellulose demonstrated predominantly Fickian mechanism of release, whereas soluble diluents (lactose and mannitol) contributed to a mixed mechanism of release. Addition of copovidone increased the swelling and survivability, whereas sodium chloride altered the erosion behavior. A correlation between matrix weight loss and drug release was obtained, which further consolidated the analysis. Correlation for the soluble excipients was linear, whereas that for the swellable excipient was nonlinear, implying predominance of Fickian release mechanism for the latter. Hence, the selection of excipients can influence matrix survivability and release kinetics, which can be used for developing GRDDS.

Drug Development and Industrial Pharmacy, 2014

Abstract Microcrystalline cellulose (MCC-102) is one of the most commonly used excipient in the p... more Abstract Microcrystalline cellulose (MCC-102) is one of the most commonly used excipient in the pharmaceutical industry. For this research purpose, authors have developed a different technique to determine the end point for MCC-102 using water and isopropyl alcohol 70% (IPA) as granulating agent. Wet and dry granules obtained were characterized for their flow properties using the powder rheometer and thermal analysis. Powder rheometer was used to measure basic flowability energy (BFE), specific energy (SE), percentage compressibility, permeability and aeration. Thermal analysis includes effusivity and differential scanning calorimetry (DSC) measurements. BFE and SE results showed water granules requires high energy as compared to IPA granules. Permeability and compressibility results suggest IPA forms more porous granules and have better compressibility as compared to water granules. Hardness data reveals interesting phenomena in which as the amount of water increases, hardness decreases and vice-versa for IPA. Optimal granules were obtained in the range of 45-55% w/w. DSC data supported the formation of optimal granules. Empirical measurements like angle of repose did not reveal any significant differences between powder flow among various granules. In this paper, with the help of thermal effusivity and powder rheology we were able to differentiate between various powder flows and determine the optimal range for granule formation.

Drug Development and Industrial Pharmacy, 2012

The effects of magnesium stearate (MgSt) polymorphs-anhydrate (MgSt-A), monohydrate (MgSt-M), and... more The effects of magnesium stearate (MgSt) polymorphs-anhydrate (MgSt-A), monohydrate (MgSt-M), and dihydrate (MgSt-D)-on rheological properties of powders were evaluated using techniques such as atomic analysis and powder rheometry. Additional evaluation was conducted using thermal analysis, micromeritics, and tableting forces. In this study, binary ratios of neat MgSt polymorphs were employed as lubricants in powder blends containing acetaminophen (APAP), microcrystalline cellulose (MCC), and lactose monohydrate (LAC-M). Powder rheometry was studied using permeability, basic flow energy (BFE), density, and porosity analysis. Thermal conductivity and differential scanning calorimetric analysis of MgSt polymorphs were employed to elucidate MgSt effect on powder blends. The impact of MgSt polymorphs on compaction characteristics were analyzed via tablet compression forces. Finally, the distribution of atomized magnesium (Mg) ions as a function of intensity was evaluated using laser-induced breakdown spectroscopy (LIBS) on tablets. The results from LIBS analysis indicated the dependency of the MgSt polymorphic forms on the atomized Mg ion intensity, with higher Mg ion intensity suggesting higher lubricity index (i.e. greater propensity to over-lubricate). The results from lubricity index suggested the tendency of blends to over-lubricate based on the MgSt polymorphic forms. Finally, tableting forces suggested that MgSt-D and MgSt-A offered processing benefits such as lower ejection and compression forces, and that MgSt-M showed the most stable compression force in single or combined polymorphic ratios. These results suggested that the initial moisture content, crystal arrangement, intra- and inter-molecular packing of the polymorphs defined their effects on the rheology of lubricated powders.

Bioorganic & Medicinal Chemistry Letters, 2010

In this research work, proline ester prodrug of acetaminophen (Pro-APAP) was synthesized and eval... more In this research work, proline ester prodrug of acetaminophen (Pro-APAP) was synthesized and evaluated for its stability in PBS buffer at various pH and Caco-2 cell homogenate. The Pro-APAP is more stable at lower pH than higher pH, with half-life of 120 min in PBS buffer at pH 2.0, half-life of 65 min at pH 5.0, and half life of 3.5 min at pH 7.4, respectively. The half-life of Pro-APAP in Caco-2 cell homogenate is about 1 min, much shorter than the half-life in PBS buffer at pH 7.4, indicating enzymes in the cell homogenate contribute to the hydrolysis of the ester bond. Carboxypeptidase A was incubated with Pro-APAP at pH 7.4 with half-life of 3.8 min which is very close to the half life in buffer itself. This clearly indicates carboxypeptidase A is not one of the enzymes contributing to the hydrolysis of the prodrug. Physicochemical characteristics such as melting point and stability of newly synthesized prodrug were determined by MDSC technique.

The purpose for the current research is to compare and evaluate physiochemical properties of spra... more The purpose for the current research is to compare and evaluate physiochemical properties of spray-dried (SD) microcrystals (MCs), nanocrystals (NCs), and nanocrystals with a dispersion agent (NCm) from a poorly soluble compound. The characterization was carried out by performing size and surface analysis, interfacial tension (at particle moisture interface), and in-vitro drug dissolution rate experiments. Nanosuspensions were prepared by media milling and were spray-dried. The SD powders that were obtained were characterized morphologically using scanning electron microscopy (SEM), polarized light microscopy (PLM), and Flowchem. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier transfer infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) for the identification of the crystalline nature of all the SD powders. The powders were characterized for their redispersion tendency in the water and in pH 1.2. Significant differences in redispersion were noted for both the NCs in both dissolution media. The interfacial tension for particle moisture interface was determined by applying the BET (Braunauer-Emmett-Teller) equation to the vapor sorption data. No significant reduction in the interfacial tension was observed between MCs and NCs; however, a significant reduction in the interfacial tension was observed for NCm at both 25 °C and 35 °C temperatures. The difference in interfacial tension and redispersion behavior can be attributed to a difference in the wetting tendency for all the SD powders. The dissolution studies were carried out under sink and under non-sink conditions. The non-sink dissolution approach was found suitable for quantification of the dissolution rate enhancement, and also for providing the rank order to the SD formulations.

AAPS PharmSciTech, 2016

Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion metho... more Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion method and characterize them for their physicochemical and performance properties. Binary mixtures of ibuprofen and poloxamer were prepared in three different ratios (1:0.25, 1:0.5, and 1:0.75, respectively) using a water-jacketed high shear mixer. In vitro dissolution and saturation solubility studies were carried out for the drug, physical mixtures, and formulations for all ratios in de-ionized water, 0.1 N HCl (pH = 1.2), and phosphate buffer (pH = 7.2). Thermal and physical characterization of samples was done using modulated differential scanning calorimetry (mDSC), X-ray powder diffraction (XRD), and infrared spectroscopy (FTIR). Flow properties were evaluated using a powder rheometer. Maximum solubility enhancement was seen in acidic media for fused formulations where the ratio 1:0.75 had 18-fold increase. In vitro dissolution studies showed dissolution rate enhancement for physical mixtures and the formulations in all three media. The most pronounced effect was seen for formulation (1:0.75) in acidic media where the cumulative drug release was 58.27% while for drug, it was 3.67%. Model independent statistical methods and ANOVA based methods were used to check the significance of difference in the dissolution profiles. Thermograms from mDSC showed a characteristic peak for all formulations with T peak of around 45°C which suggested formation of a eutectic mixture. XRD data displayed that crystalline nature of ibuprofen was intact in the formulations. This work shows the effect of eutectic formation and micellar solubilization between ibuprofen and poloxamer at the given ratios on its solubility and dissolution rate enhancement.

Nanocrystals have emerged as a potential formulation strategy to eliminate the bioavailability-re... more Nanocrystals have emerged as a potential formulation strategy to eliminate the bioavailability-related problems by enhancing
the initial dissolution rate and moderately super-saturating the thermodynamic solubility. This review contains an in-depth knowledge of,
the processing method for formulation, an accurate quantitative assessment of the solubility and dissolution rates and their correlation to
observe pharmacokinetic data. Poor aqueous solubility is considered the major hurdle in the development of pharmaceutical compounds.
Because of a lack of understanding with regard to the change in the thermodynamic and kinetic properties (i.e., solubility and dissolution
rate) upon nanosizing, we critically reviewed the literatures for solubility determination to understand the significance and accuracy of the
implemented analytical method. In the latter part, we reviewed reports that have quantitatively studied the effect of the particle size and
the surface area change on the initial dissolution rate enhancement using alternative approaches besides the sink condition dissolution.
The lack of an apparent relationship between the dissolution rate enhancement and the observed bioavailability are discussed by reviewing
the reported in vivo data on animal models along with the particle size and food effect. The review will provide comprehensive information
to the pharmaceutical scientist in the area of nanoparticulate drug delivery.

International Journal of Pharmaceutical Sciences and Research

Solvent used for preparing binder solution in wet granulation process is one of the major factors... more Solvent used for preparing binder solution in wet granulation process is one of the major factors which dictate the granule properties. Aim of our current research was to understand the effect of solvents on flow properties of Microcrystalline Cellulose granules prepared using Hydroxypropyl Methylcellulose as binder by using rheological tools and subsequently studying the effect of relative humidity on rheology of dried granules. Granules were prepared by using 2.5 %w/w binder solution in water and water: ethanol mixture (20:80v/v). Prepared granules were dried, sieved and further analyzed. Effect of relative humidity on flowability of dried granules were studied at 22%, 52%, 75% RH at room temperature for 48 hours. Modulated Differential Scanning Calorimetry and Powder rheometer was used to study the thermal and flow properties of wet, dried and humidity exposed granules. Results show that the hydro - alcoholic batches show greater resistance to flow in wet granule sta ge. But, its...

Journal of pharmaceutical sciences, Jan 26, 2015

The quantitative determination of solubility and the initial dissolution rate enhancement of crys... more The quantitative determination of solubility and the initial dissolution rate enhancement of crystalline nanoparticles were critically investigated using a separation-based approach (ultracentrifugation and filtration). Four poorly soluble model compounds (griseofulvin, celecoxib, compound-X, and fenofibrate) were used in this investigation. The effect of the stabilizer concentration on the solubility of the unmilled compound was determined first to quantify its impact on the solubility and used for comparing solubility enhancement upon nanosizing. Methodologies were established for ultracentrifugation, ensuring satisfactory separation of crystalline nanoparticles. The data obtained using separation-based methodologies proved to be accurate, reproducible, and were in fair agreement with what would be predicted from the Ostwald-Freundlich equation. The dissolution studies under sink conditions were proved to be less efficient in quantifying the initial dissolution rate of crystalline...

The objective of this research was to develop and evaluate physicochemical properties of acetamin... more The objective of this research was to develop and evaluate physicochemical properties of acetaminophen and aspirin orally disintegrating strips with high loading dose. The strips were compared with conventional over the counter strips and chewable tablets for their mechanical and chemical properties. Aspirin (81 mg) and acetaminophen (80 mg) oral dissolving films were developed with 50-55% of drug loading and were compared with GAS-X ® (62.5 mg) and chewable tablets (aspirin and acetaminophen). Orally dissolving films were developed using a solvent casting method. Sonication was proven to be a more competent step in order to load a high amount of active drug substance in the thin film strips. Different film formulations were prepared by varying concentration of polymers and plasticizers. Optimization of formulation was done by conducting studies for various mechanical properties using TA-XT plus texture analyzer. Dissolution of optimized formulation was performed in 250 ml of pH 1.2 and artificial saliva (pH 6.8). The study was conducted by stirring the dissolution media at 50 rpm, 37 C for 30 minutes and was analyzed using UV/Vis spectroscopy. The dimensions of orally dissolving films were determined with the help of vernier calipers. Modulated Differential Scanning Calorimetry (MDSC) was also performed for the filmstrips to check the compatibility. The film strip was evaluated for imperfections and cuts, peelability without rupturing, folding and cracking endurance, surface roughness, tensile strength, film burst and disintegration time with the help of TA-XT plus texture analyzer. Moisture content was performed, on the fresh, as well as stability samples. Dissolution of filmstrips showed much faster release as compared to respective chewable tablets in artificial saliva as well as in pH 1.2. Disintegration times for filmstrips were also comparable to Gas-X ® and Listerine ® . After one month stability of filmstrips at room temperature, dissolution profiles perceived with negligible change. Other mechanical properties of the filmstrips were also comparable to Gas-X ® . DSC results suggest miscibility in polymer, which explains the increase in dissolution rate of filmstrips at high dose loading. Hence, in conclusion we develop a new in house method to formulate a stable and more efficient formulation for high loading dose of aspirin and acetaminophen.

Journal of Pharmaceutical Sciences, 2011

Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic d... more Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic drugs by extending their transit time is a promising approach. Swellable systems were evaluated for this purpose. Such systems demonstrate dual mechanism of release-diffusion and erosion. GRDDS requires maintaining its dimensions, which demands diffusion as a predominant mechanism of release (Fickian). In this work, dypyridamole, a weakly basic drug, together with various grades of hydroxypropyl methylcellulose and different excipients were evaluated for release and swelling properties. Dissolution data were analyzed by curve fitting to various models to estimate predominant release mechanism. It was found that matrices containing a swellable diluent like microcrystalline cellulose demonstrated predominantly Fickian mechanism of release, whereas soluble diluents (lactose and mannitol) contributed to a mixed mechanism of release. Addition of copovidone increased the swelling and survivability, whereas sodium chloride altered the erosion behavior. A correlation between matrix weight loss and drug release was obtained, which further consolidated the analysis. Correlation for the soluble excipients was linear, whereas that for the swellable excipient was nonlinear, implying predominance of Fickian release mechanism for the latter. Hence, the selection of excipients can influence matrix survivability and release kinetics, which can be used for developing GRDDS.

Drug Development and Industrial Pharmacy, 2014

Abstract Microcrystalline cellulose (MCC-102) is one of the most commonly used excipient in the p... more Abstract Microcrystalline cellulose (MCC-102) is one of the most commonly used excipient in the pharmaceutical industry. For this research purpose, authors have developed a different technique to determine the end point for MCC-102 using water and isopropyl alcohol 70% (IPA) as granulating agent. Wet and dry granules obtained were characterized for their flow properties using the powder rheometer and thermal analysis. Powder rheometer was used to measure basic flowability energy (BFE), specific energy (SE), percentage compressibility, permeability and aeration. Thermal analysis includes effusivity and differential scanning calorimetry (DSC) measurements. BFE and SE results showed water granules requires high energy as compared to IPA granules. Permeability and compressibility results suggest IPA forms more porous granules and have better compressibility as compared to water granules. Hardness data reveals interesting phenomena in which as the amount of water increases, hardness decreases and vice-versa for IPA. Optimal granules were obtained in the range of 45-55% w/w. DSC data supported the formation of optimal granules. Empirical measurements like angle of repose did not reveal any significant differences between powder flow among various granules. In this paper, with the help of thermal effusivity and powder rheology we were able to differentiate between various powder flows and determine the optimal range for granule formation.

Drug Development and Industrial Pharmacy, 2012

The effects of magnesium stearate (MgSt) polymorphs-anhydrate (MgSt-A), monohydrate (MgSt-M), and... more The effects of magnesium stearate (MgSt) polymorphs-anhydrate (MgSt-A), monohydrate (MgSt-M), and dihydrate (MgSt-D)-on rheological properties of powders were evaluated using techniques such as atomic analysis and powder rheometry. Additional evaluation was conducted using thermal analysis, micromeritics, and tableting forces. In this study, binary ratios of neat MgSt polymorphs were employed as lubricants in powder blends containing acetaminophen (APAP), microcrystalline cellulose (MCC), and lactose monohydrate (LAC-M). Powder rheometry was studied using permeability, basic flow energy (BFE), density, and porosity analysis. Thermal conductivity and differential scanning calorimetric analysis of MgSt polymorphs were employed to elucidate MgSt effect on powder blends. The impact of MgSt polymorphs on compaction characteristics were analyzed via tablet compression forces. Finally, the distribution of atomized magnesium (Mg) ions as a function of intensity was evaluated using laser-induced breakdown spectroscopy (LIBS) on tablets. The results from LIBS analysis indicated the dependency of the MgSt polymorphic forms on the atomized Mg ion intensity, with higher Mg ion intensity suggesting higher lubricity index (i.e. greater propensity to over-lubricate). The results from lubricity index suggested the tendency of blends to over-lubricate based on the MgSt polymorphic forms. Finally, tableting forces suggested that MgSt-D and MgSt-A offered processing benefits such as lower ejection and compression forces, and that MgSt-M showed the most stable compression force in single or combined polymorphic ratios. These results suggested that the initial moisture content, crystal arrangement, intra- and inter-molecular packing of the polymorphs defined their effects on the rheology of lubricated powders.

Bioorganic & Medicinal Chemistry Letters, 2010

In this research work, proline ester prodrug of acetaminophen (Pro-APAP) was synthesized and eval... more In this research work, proline ester prodrug of acetaminophen (Pro-APAP) was synthesized and evaluated for its stability in PBS buffer at various pH and Caco-2 cell homogenate. The Pro-APAP is more stable at lower pH than higher pH, with half-life of 120 min in PBS buffer at pH 2.0, half-life of 65 min at pH 5.0, and half life of 3.5 min at pH 7.4, respectively. The half-life of Pro-APAP in Caco-2 cell homogenate is about 1 min, much shorter than the half-life in PBS buffer at pH 7.4, indicating enzymes in the cell homogenate contribute to the hydrolysis of the ester bond. Carboxypeptidase A was incubated with Pro-APAP at pH 7.4 with half-life of 3.8 min which is very close to the half life in buffer itself. This clearly indicates carboxypeptidase A is not one of the enzymes contributing to the hydrolysis of the prodrug. Physicochemical characteristics such as melting point and stability of newly synthesized prodrug were determined by MDSC technique.

The purpose for the current research is to compare and evaluate physiochemical properties of spra... more The purpose for the current research is to compare and evaluate physiochemical properties of spray-dried (SD) microcrystals (MCs), nanocrystals (NCs), and nanocrystals with a dispersion agent (NCm) from a poorly soluble compound. The characterization was carried out by performing size and surface analysis, interfacial tension (at particle moisture interface), and in-vitro drug dissolution rate experiments. Nanosuspensions were prepared by media milling and were spray-dried. The SD powders that were obtained were characterized morphologically using scanning electron microscopy (SEM), polarized light microscopy (PLM), and Flowchem. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier transfer infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) for the identification of the crystalline nature of all the SD powders. The powders were characterized for their redispersion tendency in the water and in pH 1.2. Significant differences in redispersion were noted for both the NCs in both dissolution media. The interfacial tension for particle moisture interface was determined by applying the BET (Braunauer-Emmett-Teller) equation to the vapor sorption data. No significant reduction in the interfacial tension was observed between MCs and NCs; however, a significant reduction in the interfacial tension was observed for NCm at both 25 °C and 35 °C temperatures. The difference in interfacial tension and redispersion behavior can be attributed to a difference in the wetting tendency for all the SD powders. The dissolution studies were carried out under sink and under non-sink conditions. The non-sink dissolution approach was found suitable for quantification of the dissolution rate enhancement, and also for providing the rank order to the SD formulations.