Bioequivalence of two pregabalin 300 mg capsules (Neurexal and Lyrica®) in healthy human volunteers.

The pharmacokinetics of 2 brands of pregabalin 300 mg capsules were compared in 23 healthy human volunteers after a single oral dose in a randomized cross-over study. The study protocol was prepared with relevance to the requirements set in the US FDA and the EMA guidances for conduction of bioequivalence studies. Reference (Lyrica(®), Pfizer, France) and test (Neurexal, Pharmaline, Lebanon) products were administered to fasted volunteers. Blood samples were collected up to 48 h and assayed for pregabalin using a validated LC-MS/MS method. The pharmacokinetic parameters AUC0-t, AUC0-∞, Cmax, Tmax, T1/2 and elimination rate constant were determined from plasma concentration-time profile by non-compartmental analysis method using WinNonlin V5.2. The analysis of variance did not show any significant difference between the 2 formulations and 90% confidence intervals fell within the acceptable range for bioequivalence: 80-125%. It was concluded that the 2 brands exhibited comparable pharmacokinetic profiles and that Pharmaline's Neurexal is bioequivalent to Lyrica(®) of Pfizer, France.

Water uptake by substituted amylose tablets: experimentation and numerical simulation.

BACKGROUND: Substituted amylose (SA) has been developed as excipient for direct compression matrices in the formulation of sustained release solid dosage forms. METHOD: The gel performance of SA for controlling water diffusion was studied by measuring water content in SA tablets prepared by direct compression. RESULTS: The SA gel was not freely swelling and results indicate that water content in equilibrium state was dependent on tablet size but not on compression force. The presence of electrolyte and hydrophobic lubricant played an effective role in adjusting water diffusion in SA gel. In addition, a numerical model based on finite difference method was developed that exhibits a high goodness of fit to experimental result. The output of the model was not only the macroscopic water content value but also the water distribution within SA tablets.

Quality of amoxicillin formulations in some Arab countries.

BACKGROUND AND OBJECTIVE: The problem of counterfeit and substandard drugs is recurrent in developing countries where antibiotics account for the majority of such products. The aim of this study was to investigate the quality of locally produced and imported amoxicillin products on the Lebanese, Jordanian, Egyptian and Saudi markets. METHODS: One hundred and eleven samples of amoxicillin capsules and suspensions purchased from retail pharmacies were analysed for their drug content by a validated chromatographic method in order to verify if they complied with pharmacopeial requirements. Suspensions were analysed for their drug content immediately after reconstitution as well as 7 or 14 days later according to the expiry date. RESULTS AND DISCUSSIONS: Fifty-six per cent of amoxicillin capsules did not meet the United State Pharmacopeia (USP) requirements and most had amounts bordering the lower limit. Individual average values as low as 59% of the label claim were detected. Eight per cent of the samples of suspensions gave measurements outside pharmacopeial limits. Furthermore, after 7 or 14 days, 38% of the samples were outside the pharmacopeial limits. All the European brands met the pharmacopeial limits except for one. CONCLUSION: Our results reveal the high incidence of substandard drugs on some Arab market where several factors might jeopardize the quality status of medicines: lack of effective quality assurance system during manufacture in both Arab and export countries, and uncontrolled storage conditions, especially unsuitable pharmacy premises. Use of substandard antibiotic preparations increases the risk of therapeutic failure and the emergence of drug-resistant microorganisms.

High-amylose carboxymethyl starch matrices for oral sustained drug-release: in vitro and in vivo evaluation.

High-amylose corn starch, that contains 70% of amylose chains and 30% of amylopectin, has been used to obtain substituted amylose (SA) polymers. Tablets have been prepared by direct compression, i.e. dry mixing of drug and SA, followed by compression, which is the easiest way to manufacture an oral dosage form. Until now, their controlled-release properties have been assessed only by an in vitro dissolution test. Amylose-based polymers are normally subject to biodegradation by alpha-amylase enzymes present in the gastrointestinal tract, but matrix systems show no significant degradation of tablets by alpha-amylase in vitro. High-amylose sodium carboxymethyl starch (HASCA) is an interesting excipient for sustained drug-release in solid oral dosage forms. In addition to the easy manufacture of tablets by direct compression, the results show that in vitro drug-release from an optimized HASCA formulation is not affected by either acidic pH value or acidic medium residence time. In addition, a compressed blend of HASCA with an optimized quantity of sodium chloride provides a pharmaceutical sustained-release tablet with improved integrity for oral administration. In vivo studies demonstrate extended drug absorption, showing that the matrix tablets do not disintegrate immediately. Nevertheless, acetaminophen does not seem to be the most appropriate drug for this type of formulation.

Dynamic study of the extraembryonic vascular network of the chick embryo by fractal analysis.

Fractal analysis is widely used in many scientific fields, including the study of vascularization. It is a convenient method that defines the complexity of natural structures. The chorioallantoic membrane of the chick embryo is a standard experimental model for the study of vasculogenesis and angiogenesis. The aim of this investigation was to demonstrate that fractal geometry is more appropriate than any other method to describe and analyse the evolution of a vascular network, i.e. the extraembryonar vascular network of the chick embryo. We used an original methodology to evaluate the complexity of this network in the first stages of embryo development (day 3 until 6). We demonstrated an increase of fractal dimension, indicating an increasing complexity of the vascular tree, until an asymptotical value of about 1.70 at day 4. The fractal approach is more accurate than other usual semi-quantitative or quantitative methods evaluating the complexity of a growing vascular tree.

A model of growing vascular structures.

Increasing attention is being paid to the configuration and development of vascular structures and their possible correlations with physiological events. The study of angiogenesis in normal and pathological states as well as in embryo and adult has provided new insights into the mechanism of vessel growth and organization of the vasculature. Various mathematical branching models have been developed. These constructions are mainly geometrical and only involve a branching phenomenon. We propose the use of a deterministic non-linear model based on physiological laws and hydrodynamics. Growth, branching and anastomosis, the three actual main events occurring in vascular growth, are included in this model. Space growth, including cells and vessels, is defined by a decreasing transformation. Space density and the length of new sprouts are controlled by a set of parameters. The conditions on these parameters are well established, which allows the production of realistic patterns.