Fotios M. Plakogiannis

Enhanced oral absorption of insulin from desolvated fatty acid-sodium glycocholate emulsions

Lipoidal dispersions of insulin in fatty acids were prepared using a bile salt as an emulsifier and as absorption promoter. The orally administered desolvated emulsions containing insulin-sodium glycocholate combinations showed different hypoglycemic effects depending on the fatty acid used. A palmitic acid system, containing 5 U insulin/50 mg dispersion per kg rabbit weight, resulted in the reduction of blood glucose from 105 to 75 mg/dl in 30 min. The effect extended over 150 min with statistically significant difference from non-fatty acid systems. Unsaturated fatty acids did not show the same enhancing effect as saturated fatty acids of the same carbon chain length.

Weight Variability of Pharmacist-Dispensed Split Tablets

OBJECTIVE To determine the level of weight uniformity of fragments from tablets split into halves and dispensed by pharmacists. DESIGN Pre-post comparison. SETTING Laboratory analysis of split tablets returned unused from four long-term care facilities. INTERVENTIONS Twenty-two dispensed prescriptions containing 560 split tablet halves were collected, and fragment weights (FWs) were determined. Theoretical weights (TWs) of split tablets of the same medications were determined mathematically. MAIN OUTCOME MEASURES Comparison of the mean FW with the mean TW of each dispensed prescription and determination of whether fragments met United States Pharmacopeia 24 (USP) criteria for weight variation of whole tablets. RESULTS A significant difference (P < .05) between mean TW and mean FW was found in 2 (9.1%) of the 22 dispensed prescriptions. Overall, 30 (5.4%) of 560 fragments, contained in 10 (45.5%) of the 22 dispensed prescriptions, had weights that deviated by more than 15% from the mean FW. Of the 560 fragments, 32 (5.7%), contained in 10 (45.5%) of 22 dispensed prescriptions, had weights that deviated by more than 15% from mean TW. A total of 15 (68.2%) of the 22 dispensed prescriptions had standard deviations (SDs) that were more than 6% of the mean FW. None of the TWs displayed an SD greater than the USP limit of 6%. Only 7 (31.8%) of the 22 dispensed prescriptions met USP standards, with FWs not exceeding 15% of mean FW and SDs of no greater than 6%. CONCLUSION Tablet splitting resulted in an unacceptably high incidence of weight variation. Standards should be developed to ensure uniformity of split tablets.

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...

Oral absorption of insulin encapsulated in artificial chyles of bile salts, palmitic acid and α-tocopherol dispersions

The hypoglycemic effect of orally given insulin was studied on rabbits, using different bile salts as absorption promoters, in two different carriers to form an artificial chyloform system ready to be absorbed by intestinal mucosa. The rank order of enhancement by bile salts in the presence of 1% ethanol was deoxycholate>cholate>glycocholate>glycodeoxycholate>taurodeoxycholate>no bile salts. The dose response studies with increased insulin loaded in the chyle showed a greater corresponding hypoglycemic effect with the system of cholate-palmitic-alpha-tocopherol dispersions than the cholate-palmitic acid dispersions. A more effective hypoglycemic effect was achieved using lower doses of the deoxycholate-palmitate-tocopherol-chyle dispersions.

Development and oral bioavailability assessment of a supersaturated self-microemulsifying drug delivery system (SMEDDS) of albendazole.

Objectives  Albendazoles (ABZ) poor aqueous solubility is a major determinant of its variable therapeutic response (20–50%). The purpose of this study was to develop and optimize the composition of a self‐microemulsifying drug delivery system (SMEDDS) of ABZ and assess its oral pharmacokinetics in rabbits.

Design and evaluation of transdermal chlorpheniramine maleate drug delivery system.

The study was to develop a transdermal therapeutic system for chlorpheniramine maleate (CPM). The diffusion characteristics of CPM were determined using Franz diffusion cells, from gelled ethanol-water solutions of CPM (5, 10, and 20%). TESTSKIN Living Skin Equivalent (LSE) was used to study the enhancement effect of ethanol-water solutions. The 0.6 volume fraction of ethanol gave the highest diffusion rate of CPM (Jss = 1.591 mg/cm2h). The diffusion and partition coefficient data revealed that changes in ethanol volume fraction of the vehicle and ethylene vinyl acetate (EVA) membrane characteristics directly affect CPM partitioning and diffusion across EVA membranes and EVA-pressure sensitive adhesive (PSA) laminates. The data also suggest a possible interaction of CPM with the PSA. The steady state fluxes attained with 20% CPM gel is 34 micrograms/cm2h, which is enough to keep the drug within its therapeutic plasma levels.

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 evaluation of the release of albuterol sulfate from polymer gels: Effect of fatty acids on drug transport across biological membranes

ABSTRACT In this investigation, the diffusion of the beta2 agonist albuterol sulfate (ABS) across several membranes (cellulose, hairless mouse skin, human cadaver skin) from polymer gels was studied, and the effects of several fatty acids on drug permeation through skin were evaluated. The results were then used to predict whether transdermal delivery would be appropriate for ABS. All in vitro release studies were carried out at 37°C using modified Franz diffusion cells. In preliminary studies, ABS release through cellulose membranes was studied from two polymeric gels, Klucel® (hydroxypropylcellulose) and Methocel® (hydroxypropylmethylcellulose). Three polymer concentrations were used for each gel (0.5%, 1.0%, and 1.5%). From these experiments, Klucel 0.5% was selected as the optimal formulation to study ABS diffusion across hairless mouse skin. Experiments were conducted to evaluate the effects of capric acid, lauric acid, and myristic acid as penetration enhancers. The results suggested that lauric acid preferentially enhanced ABS diffusion compared to the other fatty acids studied, and follow-up studies were done to evaluate the release through human cadaver skin from a donor containing 2% ABS and lauric acid in 0.5% Klucel®. These experiments showed that a 2:1 (lauric acid:ABS) molar ratio gave the best ABS release rates. The release rate across human cadaver skin declined slowly over 24 hr, and an average flux over 24 hr of ˜0.09 mg/hr cm2 was measured. Using this value as a steady-state flux, extrapolations predicted that transdermal delivery can be used to maintain therapeutic ABS plasma levels (6–14 ng/mL) for extended periods. The results of this research suggest that ABS is a good candidate for transdermal drug delivery.

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...