Are European marketed acyclovir 5% cream products similar? Comparison with EU and US reference product.

Objective: The aim was to perform a comparative evaluation of composition and release performance of multisource acyclovir 5% creams.

Significance: The outcome was analyzed in relation with the principles of the Topical drug Classification System (TCS).

Methods: The drug release testing (IVRT) was based on selection of an inert artificial membrane and a medium providing sink conditions, and utilizing the vertical diffusion cells.

Rheological and release measurements of manufactured acyclovir 5% creams: confirming sensitivity of the release.

Previous evaluation of marketed acyclovir 5% creams using release testing (IVRT) and its correlation with the qualitative composition confirmed the discriminative characteristics of this methodology. This was in line with the principles of Topical drug Classification System (TCS). For the current research, experimental formulations were designed and prepared by applying controlled changes in manufacturing process, sources of raw materials, and amount of the excipients.

Commonality between BCS and TCS.

Both biopharmaceutics classification system (BCS) and topical drug classification system (TCS) are based on sound scientific principles with the aim of providing biowaiver and reducing regulatory burden without lowering the quality requirements and standards of approval for the drug products. BCS is based on the solubility and permeability properties of the active pharmaceutical ingredient (API, or drug substance) whereas the TCS is based on the qualitative and quantitative composition of the dosage form and the in vitro release rate of the active ingredient as key decision tools. Both BCS and TCS take drug release and dissolution as their guiding principle for providing biowaiver, increasing the availability and affordability of safe and effective medicines to the consumers and at the same time maintaining the drug product quality.

The forgotten or underestimated relevance of biopharmaceutical-based assessments for the oral absorption studies of oxime reactivators.

Introduction: The absorption, distribution, metabolism, excretion and toxicity (ADME(T)) of oxime reactivators have been assessed with respect to their polarity, a fundamental requirement for their specific mechanism of action in the intoxication with organophosphorous compounds. The limitations of the therapeutic outcome have been associated not only with the severity of intoxication and to particularities of the toxicants, but also to the reduced lipophilicity and consequent restricted permeability across biological barriers.

Areas Covered: This article inventories the plethora of mnemotic rules developed throughout the years for defining chemical spaces where drugs share one or more structural and ADME(T) characteristics.

A science based approach to topical drug classification system (TCS).

The Biopharmaceutics Classification System (BCS) for oral immediate release solid drug products has been very successful; its implementation in drug industry and regulatory approval has shown significant progress. This has been the case primarily because BCS was developed using sound scientific judgment. Following the success of BCS, we have considered the topical drug products for similar classification system based on sound scientific principles.

Evaluation of in vitro absorption, decontamination and desorption of organophosphorous compounds from skin and synthetic membranes.

Chemical warfare agents, such as soman, and pesticides, such as chlorpyrifos, dichlorvos or malathion, are toxic organophosphorous compounds (OPCs) that are readily absorbed by the skin. Decontamination using solvents or surfactants may modify the cornified layer - the skin's main barrier against xenobiotic penetration. Thus, effective skin decontamination with fewer side effects is desired.

In vitro and in vivo evaluation of three metronidazole topical products.

Two 1% and one 0.75% metronidazole cream products were approved as bioequivalent products. These products were evaluated for their in vivo cutaneous penetration characteristics by dermatopharmacokinetic (DPK) and dermal microdialysis (DMD) sampling methodologies.

New insights on the consequences of biotransformation processes on the distribution and pharmacodynamic profiles of some neuropsychotropic drugs.

The metabolic processes frequently trigger highly complex pharmacokinetic (PK) and pharmacodynamic (PD) characteristics for the coexisting entities, parent drug and its active or inactive metabolites. The interpretation of both individual and cumulative profiles, frequently used in the therapeutic drug monitoring procedures, must take into consideration the biological coherence of the changes of the molecular descriptors characterizing the metabolites versus the parent drugs, and further qualitative and quantitative consequences on permeability processes across highly specialized biological barriers (e.g.

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review.

Undoubtedly, the use of oximes represents real progress in counteracting intoxications with organophosphates (OP), through potentiating antidotal effects of atropine. The penetration extent of these compounds through the blood-brain barrier (BBB) to significantly reactivate phosphorylated or phosphonylated acetylcholinesterase (AChE) in the brain still remains a debatable issue. Penetration of biological barriers by oximes was investigated mainly through determination of several quantitative parameters characterizing digestive absorption and BBB penetration.

The toxicokinetics and toxicodynamics of organophosphonates versus the pharmacokinetics and pharmacodynamics of oxime antidotes: biological consequences.

This paper presents basic data on organophosphonate (OP) mechanisms of action, especially by toxicokinetic/toxicodynamic (TK/TD) process correlations. It is generally accepted that at least during onset of OP biological systems interaction, blood and tissue cholinesterase's inhibition represents OP exposure marker and initiating mechanisms for toxicodynamic effects, characteristic for cholinergic crisis. OP penetrability of various biological barriers conditioning TK characteristics are determined by a series of physico-chemical properties.