Formulation and Process Development Articles

Enhancement of Iontophoretic Transport of Diphenhydramine Hydrochloride Thermosensitive Gel by Optimization of pH, Polymer Conce

The purpose of the present study was to explore the passive and electrically assisted transdermal transport of diphenhydramine hydrochloride (DPH) by iontophoresis. For better bioavailability, better patient compliance, and enhanced delivery of DPH, an iontophoretic drug delivery system of a thermosensitive DPH gel was formulated using Lutrol F-127. The study was conducted using silver–silver chloride electrodes across hairless pig skin. The effects of pH, polymer concentration, electrode design, and pulse rate on the DPH permeation were investigated. The relationship between temperature, viscosity, and conductance of DPH was correlated using conductometry. Iontophoretic transport of DPH was found to increase with a decrease in the pH of the medium and an increase in the surface area of the electrode. Viscosity measurements and flux calculations indicated the suitability of the Lutrol gel for transdermal iontophoretic delivery of DPH.

Author(s): 
Vikram Kotwal, Kiran Bhise, Rahul Thube
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Formulation and Development of Floating Capsules of Celecoxib: In Vitro and In Vivo Evaluation

The objective of the present study was to develop a hydrodynamically balanced system for celecoxib as single-unit floating capsules. Various grades of low-density polymers were used for formulation of these capsules. The capsules were prepared by physical blending of celecoxib and the polymer in varying ratios. The formulation was optimized on the basis of in vitro buoyancy and in vitro release in citrate phosphate buffer pH 3.0 (with 1% sodium lauryl sulfate). Capsules prepared with polyethylene oxide 60K and Eudragit RL100 gave the best in vitro percentage release and were used as the optimized formulation. By fitting the data into zero-order, first-order, and Higuchi models, we concluded that the release followed zero-order kinetics, as the correlation coefficient (R value) was higher for zero-order release. For gamma scintigraphy studies, celecoxib was radiolabeled with technetium-99m by the stannous reduction method.

Author(s): 
Javed Ali, Shweta Arora, Alka Ahuja, Anil K. Babbar, Rakesh K. Sharma, Roop K. Khar
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Studies on a Novel Doughnut-Shaped Minitablet for Intraocular Drug Delivery

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 32 full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days.

Author(s): 
Yahya E. Choonara, Viness Pillay, Trevor Carmichael, Michael P. Danckwerts
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Influence of Selected Formulation Variables on the Preparation of Enzyme-entrapped Eudragit S100 Microspheres

The aim of this work is to study the influence of formulation parameters in the preparation of sustained release enzyme-loaded Eudragit S100 microspheres by emulsion solvent diffusion technique. A 32 full factorial experiment was designed to study the effects of the amount of solvent (dichloromethane) and stabilizers (Tween 20, 40, or 80) on the drug content and microsphere size. The results of analysis of variance test for both effects indicated that the test is significant. The effect of amount of stabilizer was found to be higher on both responses (SSY1 = 45.60; SSY2 = 737.93), whereas solvent concentration comparatively produced significant effect on the size of microspheres (SSY1 = 0.81; SSY2 = 358.83). Scanning electron microscopy of microspheres with maximum drug content (2.5 mL dichloromethane and 0.1 mL Tween 80) demonstrated smooth surface spherical particles with mean diameter of 56.83 ± 2.88 µm.

Author(s): 
Manju Rawat, Shailendra Saraf, Swarnlata Saraf
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Estimation of the Percolation Thresholds in Lobenzarit Disodium Native Dextran Matrix Tablets

The objective of the present work is to estimate for the first time the percolation threshold of a new series of dextran (native dextran of high molecular weight [B110-1-2, Mw = 2 × 106]), in matrices of lobenzarit disodium (LBD) and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The formulations studied were prepared with different amounts of excipient in the range of 20% to 70% wt/wt. Dissolution studies were performed using the paddle method (100 rpm) and one face water uptake measurements were performed using a modified Enslin apparatus. The Higuchi, zero-order, and Hixson-Crowell models as well as the nonlinear regression model were employed as empiric methods to study the release data. Values of diffusion exponent 0.563 < n < 0.786 (Korsmeyer equation) for dissolution profile and water uptake mechanism 0.715 < n < 1 (Davidson and Peppas equation) suggested anomalous or complex mechanisms.

Author(s): 
Eddy Castellanos Gil, Antonio Iraizoz Colarte, Bernard Bataille, Isidoro Caraballo
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Production of Cromolyn Sodium Microparticles for Aerosol Delivery by Supercritical Assisted Atomization

The purpose of this study was to produce cromolyn sodium (CS) micrometric particles with controlled particle size (PS) and PS distribution (PSD) suitable for aerosol delivery, using a supercritical fluids–based process. CS was micronized using the supercritical assisted atomization (SAA) technique at different solute concentrations in water and different precipitation temperatures. Two techniques were used to measure PS and PSD of produced particles: scanning electron microscopy image analysis and laser scattering analysis. The 2 techniques were compared to provide a complete description of the powder obtained. High-performance liquid chromatography analysis was used to verify the absence of degradation of CS after micronization; differential scanning calorimetry, thermogravimetric analysis (TGA), and X-ray analysis were performed to study the effect of operative conditions on the crystalline structure and on the water content of SAA micronized particles.

Author(s): 
Ernesto Reverchon, Renata Adami, Giuseppe Caputo
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Improved Dissolution of Oleanolic Acid with Ternary Solid Dispersions

The purpose of this study was to enhance the dissolution of oleanolic acid by solid dispersions consisting of the drug, a polymeric carrier, and a surfactant. Binary solid dispersions consisting of oleanolic acid and polyvinylpyrrolidone were prepared for comparison. Polysorbate 80, a nonionic surfactant, was incorporated into binary solid dispersions as the third component to prepare ternary solid dispersions. Solid dispersions were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and dissolution tests. The crystallinization of OA was prohibited in solid dispersions. Both the binary and ternary solid dispersions enhanced the dissolution of OA. Moreover, the dissolution of ternary solid dispersion was faster compared with that of binary solid dispersion. Polysorbate 80 played an important positive role in dissolution of the solid dispersion.

Author(s): 
Longxiao Liu, Xiaocui Wang
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Formulation and Evaluation of Ethosomes for Transdermal Delivery of Lamivudine

The purpose of the present research was to investigate the mechanism for improved intercellular and intracellular drug delivery from ethosomes using visualization techniques and cell line study. Ethosomal formulations were prepared using lamivudine as model drug and characterized in vitro, ex vivo and in vivo. Transmission electron microscopy, scanning electron microscopy, and fluorescence microscopy were employed to determine the effect of ethosome on ultrastructure of skin. Cytotoxicity and cellular uptake of ethosome were determined using T-lymphoid cell line (MT-2). The optimized ethosomal formulation showed 25 times higher transdermal flux (68.4 ± 3.5 μg/cm2/h) across the rat skin as compared with that of lamivudine solution (2.8 ± 0.2 μg/cm2/h). Microscopic studies revealed that ethosomes influenced the ultrastructure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular region of deeper skin layers.

Author(s): 
Subheet Jain, Ashok K. Tiwary, Bharti Sapra, Narendra K. Jain
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Development and Evaluation of Acid-buffering Bioadhesive Vaginal Tablet for Mixed Vaginal Infections

An acid-buffering bioadhesive vaginal tablet was developed for the treatment of genitourinary tract infections. From the bioadhesion experiment and release studies it was found that polycarbophil and sodium carboxymethylcellulose is a good combination for an acid-buffering bioadhesive vaginal tablet. Sodium monocitrate was used as a buffering agent to provide acidic pH (4.4), which is an attribute of a healthy vagina. The effervescent mixture (citric acid and sodium bicarbonate) along with a superdisintegrant (Ac-Di-sol) was used to enhance the swellability of the bioadhesive tablet. The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as an antibacterial) were used in the formulation along with Lactobacillus acidophilus spores to treat mixed vaginal infections. From the ex vivo retention study it was found that the bioadhesive polymers hold the tablet for more than 24 hours inside the vaginal tube.

Author(s): 
Mohd Aftab Alam, Farhan Jalees Ahmad, Zeenat Iqbal Khan, Roop Krishen Khar, Mushir Ali
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007

Development of Prednisone:Polyethylene Glycol 6000 Fast-Release Tablets From Solid Dispersions: Solid-State Characterization, Di

The aim of the current study was to design oral fast-release polymeric tablets of prednisone and to optimize the drug dissolution profile by modifying the carrier concentration. Solid dispersions were prepared by the solvent evaporation method at different drug:polymer ratios (wt/wt). The physical state and drug:carrier interactions were analyzed by X-ray diffraction, infrared spectroscopy, and scanning electron microscopy. The dissolution rate of prednisone from solid dispersions was markedly enhanced by increasing the polymer concentration. The tablets were prepared from solid dispersion systems using polyethylene glycol (PEG) 6000 as a carrier at low and high concentration. The results showed that PEG 6000-based tablets exhibited a significantly higher prednisone dissolution (80% within 30 minutes) than did conventional tablets prepared without PEG 6000 (<25% within 30 minutes).

Author(s): 
Darío Leonardi, María Gabriela Barrera, María Celina Lamas, Claudio Javier Salomón
Journal: 
AAPS PharmSciTech ,Volume 8, Issue 4 ,2007
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