Adi I. Arida

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma using HPLC coupled with tandem mass spectrometry: Application to bioequivalence studies

A sensitive, specific and selective liquid chromatography/tandem mass spectrometric method has been developed and validated for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on a reverse phase C(18) column (50mmx4mm, 3microm) using water with 2.5% formic acid, methanol and acetonitrile (40:45:15, v/v/v (%)) as a mobile phase (flow rate of 0.70mL/min). Irbesartan and hydrochlorothiazide were ionized using ESI source in negative ion mode, prior to detection by multiple reaction monitoring (MRM) mode while monitoring at the following transitions: m/z 296-->269 and m/z 296-->205 for hydrochlorothiazide, 427-->175 for irbesartan. Linearity was demonstrated over the concentration range 0.06-6.00microg/mL for irbesartan and 1.00-112.00ng/mL for hydrochlorothiazide. The developed and validated method was successfully applied to a bioequivalence study of irbesartan (300mg) with hydrochlorothiazide (12.5mg) tablet in healthy volunteers (N=36).

Development of sustained-release ibuprofen microspheres using solvent evaporation technique

The emulsion‐solvent evaporation method was used for the preparation of ibuprofen microspheres using cellulose acetate polymer. Polyethylene glycol was used as a surfactant to improve the release properties of ibuprofen at a drug to polymer to PEG ratio of 1:2:1. The microspheres were prepared at three different speeds (800, 1200, 1600 rpm), and were characterized with regard to their surface morphology, percentage yield, average drug content, particle size distribution, and release properties in phosphate buffer pH 6.9 at 37 °C. The particles decreased with increasing stirrer speed. The formed ibuprofen microspheres were subjected to accelerated stability studies for 3 months, and the effect of the storage time on the different characteristics was studied. The physical properties and release profiles of ibuprofen microspheres did not change after storage under accelerated stability conditions for 3 months.

Cellactose® a Co-processed Excipient: A Comparison Study

This article describes the differences in compaction properties between microcrystalline cellulose (MCC) and α-lactose monohydrate physical mixture, and microcrystalline cellulose co-processed with α-lactose monohydrate (Cellactose®). The different compaction parameters are not only compared for the pure materials but also for the lubricated powders with magnesium stearate. Magnesium stearate does not facilitate the densification of either the physical mixture or Cellactose during compaction. The difference in tablet relaxation of the physical mixture and Cellactose indicates that the negative effect of the lubricant on the interparticle bonding of Cellactose particles is smaller than the physical mixture particles because after compaction, the structure in the Cellactose tablet is completely different from that in the physical mixture tablet. However, a larger increase in tablet relaxation at a high compression speed was found for both Cellactose and the physical mixture at different lubricant concentrations: 1.0% and 0.0%. Accordingly, the decrease in tablet strength was larger for the physical mixture tablets than for the Cellactose tablets when lubrication was applied. The examination of the tablet strengths of tablets compressed from physical mixtures of different ratios of α-lactose monohydrate and MCC proved the positive effect of cellulose on the tensile strength of tablets. Co-processing of MCC with α-lactose monohydrate showed extra contribution on the tablet strength of a physical mixture with the same mixing ratio. This extra contribution of Cellactose was attributed only to the interfacial attraction of the particles.

Influence of capsule shell composition on the performance indicators of hypromellose capsule in comparison to hard gelatin capsules

Abstract The purpose of this study was to assess the in vitro performances of “vegetable” capsules in comparison to hard gelatin capsules in terms of shell weight variation, reaction to different humidity conditions, resistance to stress in the absence of moisture, powder leakage, disintegration and dissolution. Two types of capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight variability was relatively low for all tested capsules shells. Although Capsule 1 had the highest moisture content under different humidity conditions, all capsule types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone (PVP) powder from surrounding humidity. The initial disintegration for all Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n = 18). Dissolution of acetaminophen was better when the deionized water (DIW) temperature increased from 32 to 42 °C in case of Capsule 1, but the effect of temperature was not significant for the other types of capsules. Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and independent of the media pH or contents unlike Capsule 2 which was influenced by the pH and dissolution medium contents. It is feasible to use hypromellose capsules shells with or without gelling agent for new lines of pharmaceutical products, however, there is a window for capsule shells manufacturing companies to improve the dissolution of their hypromellose capsules to match the conventional gelatin capsule shells and eventually replace them.

Effect of the Lubricant Magnesium Stearate on Changes of Specific Surface Area of Directly Compressible Powders under Compression = تأثير المشحم ( مغنيسيوم ستياريت ) على تغيرات المساحة السطحية الخاصة بالمساحيق القابلة للكبس أثناء عملية الكبس

During compression, powders fragment, plastically deform, and/or may behave both ways. Different profiles of specific surface area changes have been shown in several studies for many powders. In this study, the effect of a lubricant on the specific surface area of a powder was studied during the consolidation process of the powder as an attempt to clarify the behavior of powders under compression. Changes in specific surface areas of Starch (Rice starch), cellulose (Avicel ® PH102), spray dried lactose (Zeparox ® ), and dibasic calcium phosphate (Emcompress ® ) were studied using gas adsorption technique. Magnesium stearate was used as a lubricant. Specific surface area of plastically deforming materials; cellulose, and starch was clearly affected by the addition of lubricants. Spray dried lactose combined both fragmenting and plastically deforming behavior in its consolidation under compression and its specific surface area was slightly affected by the addition of lubricant. Specific surface area of fragmenting material; Dibasic calcium phosphate was not affected by the addition of a lubricant.