A. Babar

Controlled-release naproxen using micronized ethyl cellulose by wet-granulation and solid-dispersion method

ABSTRACT This study has been undertaken to develop a controlled-release tablet dosage form of naproxen using ethocel (ethyl cellulose) as the rate-controlling polymer. The formulations were made by employing the conventional wet-granulation method and the solid-dispersion method. Tablets made by both methods were compared for their controlled-release dissolution profiles. Both methods were useful in developing the controlled-release formulations of naproxen with desirable properties. However, the amount of polymer required to make a formulation with the desired release profile was 33% less via solid dispersion than via wet granulation. A cumulative 88% of naproxen was released from the solid-dispersion formulation, compared with 84% from the wet-granulation formulation.

Piroxicam Release from Dermatological Base: In-Vitro Studies using Cellulose Membrane and Hairless Mouse Skin

AbstractPiroxicam is one of the most potent non-steroidal, anti-inflammatory agents which also exhibits antipyretic activity. Piroxicam is well absorbed following the oral administration, however, its use has been associated with a number of gastro-intestinal disorders including bleeding and ulceration. To overcome these side effects, this study was undertaken to develop diadermatic dosage form using various polymeric gel and ointment bases containing 1% piroxicam were prepared to study the in-vitro release of the drug. Also, a series of additive ingredients, such as, alcohol USP, polyethylene glycol-400 and dimethyl sulfoxide (DMSO) were incorporated in these formulations at various concentration levels to evaluate their effects on drug release. The general rank order for the in-vitro drug release from all the bases evaluated was: gel base > hydrophillic base > emulsion base. In general, additives had little or no effect in enhancing the drug release from these bases. The in-vitro release data were treat...

Ketoprofen Suppository Dosage Forms: In Vitro Release and in Vivo Absorption Studies in Rabbits

In vitro release of ketoprofen from suppository bases and in vivo absorption in rabbits were studied. Suppositories containing 50 mg of ketoprofen were prepared using theobroma oil, esterified (c10-c18) fatty acids, and polyethylene glycol 1000 bases. The displacement values of the drug were determined and found to be of the order of theobroma oil > esterified (c10-c18) fatty acids and polyethylene glycol 1000 bases. The suppository hardness data revealed that the theobroma oil base produced relatively brittle suppositories. Using the USP dissolution method, the release of ketoprofen was observed to be greatest from polyethylene glycol 1000 suppositories. With the dialysis technique, the maximum release of drug was obtained from theobroma oil suppository containing polysorbate 40 at a 6% level. Selected suppository formulations were evaluated for rectal absorption studies in rabbits. The in vivo data showed that the optimum drug absorption took place from the polyethylene glycol 1000 base and theobroma oil formulation containing 6% polysorbate 40.

Medicament Release From Ointment Bases: V. Naproxen In-Vitro Release and In-Vivo Percutaneous Absorption In Rabbits

AbstractThe in- vitro release of Naproxen from various ointment bases, including a water-washable base with the drug in the water phase (I) and the drug in the oil phase (II), a hydrophilic base with the drug in the water phase (III), and the drug in the oil phase (IV), and an anhydrous ointment (V), a gel (VI) and a modified University of California (U.C.H.) base (VII) were studied. In addition, the effects of various additives (urea, ethanol, dimethyl sulfoxide and polyethylene glycol-400) on the release of Naproxen from formulations (I) and (II) were determined. Low concentrations of urea and ethanol in the formulations increased the release of the drug from both these bases, however, higher concentrations adversely affected the release of the drug. While dimethyl sulfoxide (DMSO) had no significant effect on the drug release, the inclusion of polyethylene glycol-400 in both bases decreased the release of Naproxen.The percutaneous absorption of Naproxen from the waterwashable base (drug in the oil phas...

In-Vitro Release Studies of Chlorpheniramine Maleate from Topical Bases Using Cellulose Membrane and Hairless Mouse Skin

AbstractIn-vitro release of chlorpheniramine maleate from various topical bases was studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included a polymer gel base, a modified hydrophilic ointment base and a modified petrolatum base. The effects of the additive ingredients, such as, urea, ethanol and dimethylsulfoxide (DMSO) on the drug release were also investigated. The rank order of drug release through the cellulose membrane was observed to be: the gel base > the modified hydrophilic ointment base > the modified hydrophilic petrolatum base. In general, the presence of additives adversely affected the drug release except for the (DMSO) and ethanol in certain cases.The samples with maximum drug release through the cellulose membrane were further studied for the drug release using hairless mouse skin as the diffusion barrier. Here again, the gel base gave the best in-vitro release of the drug, and the data correlated well with the results obtained through the cellulo...

Medicament Release from Ointment Bases: III. Ibuprofen: In Vitro Release and In-Vivo Absorption in Rabbits

AbstractThe in-vitro release of ibuprofen from various topical bases including: water-washable base, hydrophilic base, cream, Canadian formulary base, gel, emulsion, water-soluble base and University of California Hospital base were studied. Also, the effects of the additives (ethanol, polyethylene glycol—400, urea and dimethylsulfoxide) on the release rate of the drug from the water-washable base were evaluated.In general, the in-vitro release rate rank order of the drug was observed to be: water-washable base > hydrophilic base > Canadian formulary base > gel > PEG water washable > emulsion > cream > University of California base. The additive ingredients had a Little or no effect in enhancing the release of drug from the samples studied.The formulations with optimum in-vitro drug release were scaled up for in-vivo percutaneous absorption in rabbits. The blood samples were analyzed by a HPLC method. Among the candidates evaluated in-vivo, the bioavailability of the drug was significantly higher from the...

In vitro release and diffusion studies of promethazine hydrochloride from polymeric dermatological bases using cellulose membrane and hairless mouse skin.

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.

Fluidized-Bed agglomeration of acetaminophen; direct compression of tablets and physiologic availability

AbstractA novel process was developed for manufacturing acetaminophen in a free-flowing, directly compressible agglomerated form, involving spray agglomeration of acetaminophen powder with polyvinylpyrrolidone (PVP) in isopropyl alcohol as a bonding agent using a fluidized-bed granulator. Agglomerates prepared with 5% PVP yielded a free-flowing and compressible material. Upon lubrication with 0.5% magnesium stearate, the material was found to be directly compressible into tablets. To improve dissolution and tableting properties, the agglomerates were compressed into tablets after blending with varying weight ratios of microcrystalline cellulose/pregelatinized starch as a filler/disintegrant combination. The final stable tablet formulation consisted of agglomerates equivalent to 325 mg of acetaminophen, 2.1 mg of magnesium stearate, and the filler/disintegrant in a weight ratio of 70:30 to yield a tablet weight of 425 mg. Physical properties and dissolution profile of these tablets were comparable to those...

Release and permeation studies of propranolol hydrochloride from hydrophilic polymeric matrices

AbstractIn-vitro release of propranolol hydrochloride, from various hydrophilic polymeric bases was studied. These included: methocel®, avicel® CL-611/ methylcellulose, polyvinyl alcohol/gelatin based systems. Several additives, such as, ethyl alcohol, dimethylsulfoxide (DMSO) and polyethylene glycol-400 were included in the formulations for possible enhancement of the drug release. The release studies were carried out using the cellulose membrane and the hairless mouse skin as the diffusion barriers. The general rank order for the drug release through these membranes was observed to be: the methocel® matrix > the avicel® CL-611 matrix > the polyvinyl alcohol/gelatin matrix > and the emulsion base. The additives in the formulations had little or no effect in enhancing the drug release. However, when the hairless mouse skin was soaked in (DMSO) for one hour prior to its use in the diffusion studies, the drug release was found to increase by 40% from the methocel® matrix formulation.The drug release data we...

In-Vitro Release of Zinc Pyrithione from A Shampoo Base and the Effects of Various Additives on its Release Rate

AbstractZinc pyrithione has been established as one of the most effective anti-dandruff ingredients for use in shampoo formulations, through various clinical studies. However, the clinical efficacy is dependent upon its release rate from the vehicle and adsorption onto the scalp and hair. In light of these findings, the release of zinc pyrithione from a typical lotion shampoo base was investigated in-vitro. The shampoo formulation consisted of an anionic detergent, an amide and thickening agents commonly used in such products. The additives used included ethanol, dimethylsulfoxide (DMSO), polyethylene glyeol-400, propylene glycol and urea at 5%, 10% and 15% by weight of the formulations.Release experiments were carried out at 37°C, with diffusion cells immersed in beakers containing distilled water adjusted to pH 5.In general, the presence of the additive ingredient increased the release of zinc pyrithione. Among the samples evaluated, the formulations containing ethanol or propylene glycol gave the highe...