Dissolution Profiles Of Formulations Research Articles

Assessment of physical and dissolution characteristics of various itraconazole capsule formulations: a comparative analysis

<p class="abstract"><strong>Background:</strong> This <em>in vitro</em> study compared physical parameters and the dissolution profile of innovator itraconazole capsule formulation, i-Tyza, and 5 other generic capsule formulations available in the Indian market.</p><p class="abstract"><strong>Methods:</strong> The number of pellets and size distribution were determined using naked eye examination and sieving method, respectively. Dissolution profile of formulations was done at 15, 30, 45, and 60 minutes, using a United States Pharmacopeia type II Paddle apparatus in simulated gastric fluid (SGF, pH 1.2) without enzymes, acetate buffer (pH 4.5) with 0.5% sodium lauryl sulfate (SLS), and phosphate buffer (pH 6.8) with 0.5% SLS.<strong></strong></p><p class="abstract"><strong>Results:</strong> All formulations had capsule size 0. Capsule fill weight (~335 to ~510 mg) and total pellet number (127 to 810) varied across formulation, with the innovator brand having the highest number of pellets. Innovator product and i-Tyza had similar fill weight (~460 mg). Pellet size distribution of the innovator product, brand 2, brand 3, and i-Tyza was relatively narrow. In SGF, except brand 1 (84% dissolved) and brand 5 (80% dissolved), all the formulations had near-complete (>85% drug dissolved) or complete dissolution (>90% drug dissolved) at 60 minutes. In acetate buffer, pH 4.5 with 0.5% SLS and phosphate buffer, pH 6.8 with 0.5% SLS, only the innovator product and i-Tyza demonstrated near-complete to complete dissolution at 60 minutes (96% and 90% dissolved).</p><p class="abstract"><strong>Conclusions:</strong> Across all the itraconazole generic formulations evaluated, i-Tyza had comparable physical characteristics and dissolution profile to the innovator product. The <em>in vitro</em> dissolution profile of i-Tyza may indicate adequate <em>in vivo</em> performance.</p>

THE INFLUENCE OF HPC-L AND EUDRAGIT L30 D-55 ON DELAYED RELEASE OMEPRAZOLE MAGNESIUM MULTIPLE-UNIT PELLET SYSTEM

Objective: The objective of the study is to develop optimum, stable, delayed release pellets of omeprazole magnesium (20.6 mg dose). Omeprazole magnesium is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+ -ATPase at the secretory surface of the gastric parietal cell, which is orally administered drug, whereas omeprazole magnesium is degraded in stomach pH, so it is formulated as delayed release dosage form to absorb in intestinal pH.Methods: The formulation of delayed release pellets of omeprazole magnesium was developed by enteric film coating process varying the compositions of drug loading, barrier coating, and enteric coating using fluid bed processor. The prepared multiple pellets were filled into hard gelatin capsules as a single unit dosage forms.Results: The dissolution profile of formulation (F8) contains the efficient amount of hydroxypropyl cellulose-L and Eudragit L30 D55 leads to effective release of drug in 30 min. Fourier transform infrared and differential scanning colorimeter studies were conducted for the optimized formula to prove that the formula was not having incompatibility between the drug and excipients. The scanning electron microscopy studies were conducted to know the surface morphology of the pellets.Conclusion: It was concluded that optimized formulation (F8) shown good similarity with innovator. The results of the accelerated stability of final formulation revealed that storage conditions were excellent.

HPLC determination of olanzapine and carbamazepine in their nicotinamide cocrystals and investigation of the dissolution profiles of cocrystal tablet formulations

Cocrystals have recently gained importance in the pharmaceutical industry. In this study, olanzapine and carbamazepine cocrystals were synthesized by using nicotinamide as cocrystal forming agent to achieve improvements in the physicochemical characteristics of the active ingredients. An HPLC method was developed to determine the amount, thus, the stoichiometric ratios of olanzapine and carbamazepine in the synthesized cocrystals. Olanzapine:nicotinamide and olanzapine tablet formulations were prepared and the developed HPLC method was applied successfully in order to compare the dissolution profiles of these formulations. An ACE 5 CN, 25 cm × 4.6 mm, 5 µm column was used and a gradient elution program was performed for simultaneous determination of olanzapine, carbamazepine and nicotinamide. Phosphate buffer (pH 5.0, 25 mM) and methanol was used in a ratio from 80:20 to 70:30 while the flow rate was 1 mL min−1 for the elution of the compounds within 12 min. In conclusion, two different aims were achieved, the first one was to indicate the stoichiometric ratios of the active ingredients olanzapine and carbamazepine with nicotinamide in their cocrystals, and the second one was the comparison of the dissolution profiles of the olanzapine and olanzapine:nicotinamide cocrystal formulations. It was found that the cocrystal formulation with nicotinamide improved the dissolution profile of olanzapine.

Dissolution enhancement of Tibolone by micronization technique

Objectives: Tibolone is an estrogen-like compound used for the treatment of the symptoms associated with the menopausal transition and also for the treatment of osteoporosis. The aim of this study was to evaluate impact of micronization on the dissolution profile so as to improve the release rate of Tibolone drug from tablet dosage form. Materials and Methods: Tibolone oral tablet 2.5 mg is formulated using micronized and unmicronized drug in a preoptimized formula and was evaluated for drug content, dissolution, hardness, thickness, and disintegration time. Particle size reduction of Tibolone drug was achieved by Air Jet Milling and evaluated by using Malvern mastersizer instrument. Results: Micronization of Tibolone enhanced its dissolution rate to a significant extent when compared with unmicronized material. The dissolution profile of formulation with micronized Tibolone was similar to that of European market product (Livial tablet 2.5 mg). Conclusion: Micronization technique has a significant impact on the dissolution of Tibolone. The experimental findings suggest that micronization can be used for the preparation of rapidly dissolving formulations of Tibolone, and could potentially lead to improvement in the in-vivo bioavailability of Tibolone oral tablets.

Comparison of Dissolution Profiles and Serum Concentrations of Two Lamotrigine Tablet Formulations

Objective: The aim of this study was to investigate the extent of variations in lamotrigine serum concentrations between two immediate-release tablet formulations. Data were compared with in vitro difference and similarity tests on dissolution profiles of the two formulations.Methods: Dissolution characteristics of formulations A (reference) and B (test) were evaluated at three points spanning the physiologic pH range (pH 1.2, pH 4.5, pH 6.8). A model-independent approach of difference (f1) and similarity (f2) tests were applied to dissolution data. A clinical study was performed with 16 patients who were divided into two groups — one group received formulation A (n=9) and the other received formulation B (n=7). Lamotrigine steady-state concentrations were determined by high-performance liquid chromatography on a reverse-phase column.Results: There were no statistically significant differences in lamotrigine serum concentrations between the two groups, although formulation B had slightly higher mean concentration values (formulation A: 3.97±4.1 μg/mL; formulation B: 5.78±2.7 μg/mL). Dissolution profiles of the two formulations were similar in the pH 1.2 dissolution medium; however, the dissolution profiles of formulation B were outside the dissolution limit (≥85% at 15 minutes) in the pH 4.5 and 6.8 dissolution media.Conclusions: No significant changes in the serum concentrations of lamotrigine were seen between the two investigated formulations. There is no evidence to suggest that the differences in dissolution profiles at pH 4.5 and pH 6.8 affect the therapeutic efficacy of the formulations. It is evident that the doses of test formulation given to the patients were higher as a consequence of common assumption that generic products have a lower absorption rate, which is proven unnecessary in this study. This investigation was a pilot study and thus further investigations with a larger sample size are necessary to determine if there is a connection between dissolution profiles and the therapeutic effect of investigated formulations.

Comparison of Dissolution Profiles and Serum Concentrations of Two Lamotrigine Tablet Formulations

Objective: The aim of this study was to investigate the extent of variations in lamotrigine serum concentrations between two immediate-release tablet formulations. Data were compared with in vitro difference and similarity tests on dissolution profiles of the two formulations. Methods: Dissolution characteristics of formulations A (reference) and B (test) were evaluated at three points spanning the physiologic pH range (pH 1.2, pH 4.5, pH 6.8). A model-independent approach of difference (f1) and similarity (f2) tests were applied to dissolution data. A clinical study was performed with 16 patients who were divided into two groups — one group received formulation A (n=9) and the other received formulation B (n=7). Lamotrigine steady-state concentrations were determined by high-performance liquid chromatography on a reverse-phase column. Results: There were no statistically significant differences in lamotrigine serum concentrations between the two groups, although formulation B had slightly higher mean concentration values (formulation A: 3.97±4.1 μg/mL; formulation B: 5.78±2.7 μg/mL). Dissolution profiles of the two formulations were similar in the pH 1.2 dissolution medium; however, the dissolution profiles of formulation B were outside the dissolution limit (≥85% at 15 minutes) in the pH 4.5 and 6.8 dissolution media. Conclusions: No significant changes in the serum concentrations of lamotrigine were seen between the two investigated formulations. There is no evidence to suggest that the differences in dissolution profiles at pH 4.5 and pH 6.8 affect the therapeutic efficacy of the formulations. It is evident that the doses of test formulation given to the patients were higher as a consequence of common assumption that generic products have a lower absorption rate, which is proven unnecessary in this study. This investigation was a pilot study and thus further investigations with a larger sample size are necessary to determine if there is a connection between dissolution profiles and the therapeutic effect of investigated formulations.

Sterilized ibuprofen-loaded poly(D,L-lactide-co-glycolide) microspheres for intra-articular administration: effect of γ-irradiation and storage

The aim of this study was to prepare and characterize a controlled-release system (microspheres) loaded with ibuprofen, for intra-articular administration, to extend its anti-inflammatory effect in the knee joint cavity. Among the bioresorbable polymers employed, poly(D,L-lactic-co-glycolic) acid (PLGA) (13 137 Da) was chosen because of its high biocompatiblity. Microspheres were produced by the solvent evaporation process from an O/W emulsion. Labrafil M 1944 CS was included in the formulation as an additive in order to modulate the release rate of the non-steroidal anti-inflammatory drug (NSAID). Once prepared, the microspheres were sobre-sterilized by γ-irradiation. The effect of the irradiation dose (25 kGy) exposure, at low temperature, on the formulation was evaluated. The sterilization procedure employed did not alter the physico-chemical characteristics of the formulation. Dissolution profiles of formulations behaved similarly and overlapped (f2 = 87.23, f1 = 4.2) before and after sterilization. Size Exclusion Chromatography (SEC) revealed no significant changes in the polymer molecular weight. Additionally, a stability study of the sterilized formulation was carried out using microsphere storage conditions of 4°C in a vacuum desiccator for 1 year. The results obtained after storing the sterilized microspheres show no significant alterations in the ibuprofen release rate (f2 = 85.06, f1 = 4.32) or in the molecular weight of the PLGA (12 957 Da). The employment of low molecular weight PLGA polymers resulted as advantageous, due to the practical absence of degradation after gamma irradiation (25 kGy) exposure at low temperature.

Study of the Influence of the pH Media Dissolution, Degree of Polymerization, and Degree of Swelling of the Polymers on the Mechanism of Release of Diltiazem from Matrices Based on Mixtures of Chitosan/Alginate

ABSTRACTThe dissolution profiles of formulations based on mixtures of chitosan/alginate depend on the pH. It is possible to distinguish two processes: (a) a fast kinetic drug release up to 180 min, where the pH value changes from 1.17 to 2.21 and the drug released is controlled by the degree of polymerization and the quantity of chitosan in the formulation; (b) a low kinetic drug release between 210 and 480 min, where the pH value changes from 5.52 to 8.72 and the drug release from the matrix is controlled by the interpolymeric complex. In all formulations the order of release, according to Peppas's model in the range of fast kinetic drug release, was between 0.5 and 1.0. The mechanism of release was non-fickian diffusion, which corresponds to a coupling mechanism of diffusion and relaxation of the polymer.

Biodegradable PLGA microspheres loaded with ganciclovir for intraocular administration. Encapsulation technique, in vitro release profiles, and sterilization process.

The purpose of this work was to obtain a sterilized formulation consisting of biodegradable microspheres of poly (DL-lactide-co-glycolide) (PLGA) for intraocular sustained release of ganciclovir. Microspheres were prepared using a dispersion of ganciclovir in fluorosilicone oil (FSiO) that was further dispersed in an acetone solution of PLGA [50/50 and inherent viscosity 0.41 dl/g], and emulsified in silicone oil with a surfactant. Once prepared, the formulation was exposed with an effective gamma radiation dose of 2.5 megarads. The release rate data of ganciclovir from the sterilized and nonsterilized batches were compared using the similarity factor (f2). The dispersion of the drug in FSiO contributed to achieving a drug payload of up to 95% of the theoretical in the 300-500 microm microspheres. Ten mg released ganciclovir in vitro at 1.3 microg/h for the first 21 days, but decreased to approximately 0.2 microg/h from day 25 until the end of the release study (42 days). No significant differences in the amounts of encapsulated drug (alpha = 0.05) were observed between the sterilized and nonsterilized microspheres. Furthermore, dissolution profiles of formulations behaved similarly before and after gamma radiation exposure. The technique of microsphere preparation described resulted in high ganciclovir loading (95%) and prolonged drug release. The ganciclovir formulation behaved similarly before and after the sterilization process.

Formulation of Once a Day Controlled Release Tablet of Indomethacin Based on HPMC-Mannitol

p>A hydroxypropyl methylcellulose (HPMC K4M, HPMC K15M, and HPMC K100M) matrix tablet containing Indomethacin along with mannitol was formulated as a function of HPMC viscosity, and was compared with the commercial products. The release characteristics of the matrix tablet were investigated in the intestinal fluid, 6.8 pH phosphate buffer for 12 hours. The formulated products and two marketed products as reference sample were studied for its different physicochemical parameters and in vitro dissolution studies. It was found that the drug release profile decreases with increase in viscosity of polymer and, with increase polymer level in the formulations. Matrix tablets formulated employing Drug:HPMC K15M:mannitol::1:0.25:1 and Drug:HPMC K15M:mannitol::1:0.25:2 gave slow release of indomethacin spread over 12 hours and their dissolution profiles were compared with the Indian marketed product. The dissolution profiles of both the formulations were similar to the dissolution profile of the marketed product, the similarity factor being 74.59 and 68.04 respectively. The dissolution profiles of formulations containing same viscosity grade of HPMC in remarkably different concentrations and different viscosity grade of HPMC in same concentrations were different. Key words: Indomethacin; Controlled release; Hydroxypropyl methyl cellulose; Mannitol; Dissolution. DOI: 10.3126/kuset.v4i1.2884 Kathmandu University Journal of Science, Engineering and Technology Vol.4, No.1, September 2008, pp 55-67