Development and Application of a High-Performance Liquid Chromatography Stability-Indicating Assay for Beyond-Use Date Determination of Compounded Topical Gels Containing Multiple Active Drugs.

Topical gels compounded by pharmacists are important clinical tools for the management of pain. Nevertheless, there is often a dearth of information about the chemical stability of drugs included in these topical formulations, complicating the assignment of beyond-use dating. The purpose of this study was to develop a high-performance liquid chromatography photodiode array-based stability-indicating assay that could simultaneously resolve six drugs (amitriptyline, baclofen, clonidine, gabapentin, ketoprofen, lidocaine) commonly included in topical gels for pain management and their potential degradation products.

Stability of an Extemporaneously Compounded Oral Suspension of Bosentan.

Purpose: To assess the stability of an extemporaneously compounded oral suspension of bosentan from commercially available tablets for a period of 1 month.

Methods: A 6.25 mg/mL oral suspension of bosentan monohydrate was prepared from Tracleer tablets.

Chiral stability of an extemporaneously prepared clopidogrel bisulfate oral suspension.

Objectives: The purpose of this study was to evaluate the chiral stability of clopidogrel bisulfate in an extemporaneously compounded oral suspension for a period of 60 days.

Methods: A 5 mg/mL oral suspension of clopidogrel bisulfate was prepared from commercially available Plavix tablets. The clopidogrel suspension was then evenly divided between two light-resistant prescription bottles and stored either under refrigeration (4°C) or at room temperature (25°C).

Rho-kinase inhibitors offer a new approach in the treatment of glaucoma.

Introduction: Primary open-angle glaucoma (POAG) is a leading cause for worldwide blindness and is characterized by progressive optic nerve damage. The etiology of POAG is unknown, but elevated intraocular pressure (IOP) and advanced age have been identified as risk factors. IOP reduction is the only known treatment for glaucoma.

Effect of formulation pH on transdermal penetration of antiemetics formulated in poloxamer lecithin organogel.

The purpose of this study was to assess the impact of altering formulation pH on the transdermal penetration of several commonly used antiemetic, weakly basic drugs incorporated into poloxamer lecithin organogel vehicle. Poloxamer lecithin organogel formulations containing promethazine hydrochloride (25 mg/mL), metoclopramide hydrochloride (10 mg/mL), and ondansetron hydrochloride (8 mg/mL) were examined for both drug release and transdermal penetration across porcine skin in modified Franz diffusion cells for a period of 24 hours. For the transdermal studies, each antiemetic drug was formulated at a pH above and below their acid dissociation constant (pKa) in an attempt to assure that the drug would be primarily in their respective ionized or non-ionized states.

The effect of Rho-associated kinase inhibition on the ocular penetration of timolol maleate.

Purpose: To assess the effects of Rho-associated kinase (ROCK) inhibition on the intraocular penetration of timolol maleate.

Methods: Ex vivo porcine corneal penetration of timolol maleate, sotalol hydrochloride, or brinzolamide incubated with or without Y-27632 was determined in vertical Franz diffusion cells. The effect of ROCK inhibition on the vasodilation of porcine conjunctival vasculature was assessed by scanning electron microscopy (SEM) and immunohistochemical staining with subsequent laser-scanning confocal microscopy (LSCM).

Reestablishment of the nasal permeability barrier to several peptides following exposure to the absorption enhancer tetradecyl-beta-D-maltoside.

Regular insulin, NPH insulin, glargine insulin, calcitonin, and human growth hormone were administered to rats nasally with 0.125% tetradecyl-beta-D-maltoside (TDM), or at various times after TDM treatment. Absorption of all five peptides was enhanced initially and diminished in a time-dependent manner as the interval between administration of TDM and the peptide increased.

The release and transdermal penetration of baclofen formulated in a poloxamer lecithin organogel.

The purpose of this study was to evaluate the in vitro release and ex vivo penetration of baclofen following incorporation into a 2% poloxamer lecithin organogel. Franz cells were utilized for both the release and penetration studies. Semi-permeable dialysis membranes were used as the model skin for the penetration study.

Eyedrops containing SA9000 prodrugs result in sustained reductions in intraocular pressure in rabbits.

Aim: Poor topical bioavailability and ocular irritation have impeded the development of the diuretic, ethacrynic acid (ECA) as a clinically useful ocular hypotensive for the treatment of glaucoma. Thus, the development of analogs and prodrugs of analogs with improved ocular penetration, potency, and tolerability is required. The aim of this work is to evaluate the corneal penetration and ocular distribution of SA9000, an ECA analog.

Tetradecylmaltoside (TDM) enhances in vitro and in vivo intestinal absorption of enoxaparin, a low molecular weight heparin.

Tetradecylmaltoside (TDM) was evaluated as a potential gastrointestinal absorption enhancer for low molecular weight heparin (LMWH), enoxaparin. The in vitro efficacy of TDM (0.0625, 0.

Correlation of tetradecylmaltoside induced increases in nasal peptide drug delivery with morphological changes in nasal epithelial cells.

The effect of tetradecylmaltoside (TDM) on nasal peptide drug absorption was assessed with four peptides of distinct molecular size: insulin (5.7 kDa), leptin (16 kDa), somatropin (22.1 kDa), and epoetin alfa (30.

Absorption enhancers in pulmonary protein delivery.

Extensive research efforts have been directed towards the systemic administration of therapeutic proteins and poorly absorbed macromolecules via various nontraditional, injection-free administration sites such as the lung. As a portal for noninvasive delivery, pulmonary administration possesses several attractive features including a large surface area for drug absorption. Nevertheless, achieving substantial bioavailability of proteins and macromolecules by this route has remained a challenge, chiefly due to poor absorption across the epithelium.

Effects of the permeability enhancers, tetradecylmaltoside and dimethyl-beta-cyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o-).

The permeability of human bronchial epithelial cells (16HBE14o(-)) to radiolabelled insulin ([125I]insulin) formulated in the absence or presence of two different saccharide-containing permeability enhancers was investigated. In the absence of either enhancer, mannitol permeability and transepithelial electrical resistance (R(TE)) remained essentially unaffected for the duration of a 2-h experiment. Addition of either 0.

Sucrose cocoate, a component of cosmetic preparations, enhances nasal and ocular peptide absorption.

Sucrose cocoate (SL-40), an emulsifier employed in emollient, skin-moisturizing cosmetic formulations, contains a mixture of sucrose esters of coconut fatty acids in aqueous ethanol solution. In order to determine its potential utility in enhancing nasal and ocular drug delivery, absorption studies were performed in anesthetized Sprague-Dawley male rats with calcitonin and insulin, two distinct therapeutic peptides. Administration of a nasal insulin formulation containing 0.

Synthetic long-chain alkyl maltosides and alkyl sucrose esters as enhancers of nasal insulin absorption.

A series of new glycosides with extended alkyl side-chains (C(13-16)) linked to maltose or sucrose were synthesized and tested for their efficacy in enhancing nasal insulin absorption in anesthetized rats. The new reagents were compared to previously tested alkylglycosides with shorter alkyl side chains (C(8-12)). Dose-response studies revealed that within the family of alkylmaltoside derivatives, (C(8-16)), maximal increases in insulin absorption took place when tetradecylmaltoside (C(14)) was added to the formulation.