Dizajniranje i evaluacija dvoslojnih plutajućih tableta kaptoprila

The objective of the present investigation was to develop a bilayer-floating tablet (BFT) for captopril using direct compression technology. HPMC, K-grade and effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained captopril and various polymers such as HPMC-K15M, PVP-K30 and Carbopol 934p, alone or in combination with the drug. The floating behavior and in vitro dissolution studies were carried out in a USP 23 apparatus 2 in simulated gastric fluid (without enzyme, pH 1.2). Final formulation released approximately 95% drug in 24 h in vitro, while the floating lag time was 10 min and the tablet remained floatable throughout all studies. Final formulation followed the Higuchi release model and showed no significant change in physical appearance, drug content, floatability or in vitro dissolution pattern after storage at 45 oC/75% RH for three months. Placebo formulation containing barium sulphate in the release layer administered to human volunteers for in vivo X-ray studies showed that BFT had significantly increased the gastric residence time.U radu je opisana priprava dvoslojnih plutajućih tableta (BFT) kaptoprila metodom izravne kompresije. Plutajući dio tablete izrađen je iz HPMC, K-sloja i efervescentne smjese limunske kiseline i natrijevog bikarbonata. Sloj s aktivnom supstancijom sadrži kaptopril i različite polimere kao što su HPMC-K15M, PVP-K30 i Crbopol 934p,sam ili u smjesi s ljekovitom tvari. Sposobnost plutanja i in vitro oslobađanje ispitivano je u aparaturi 2 prema USP XXIII u simuliranom želučanom soku (bez enzima, pH 1,2). Iz pripravljenih tableta oslobodilo se približno 95% ljekovite tvari tijekom 24 h u navedenim in vitro uvjetima, a floating lag time bilo je 10 min. Tablete su plutale tijekom cijelog pokusa. Pripravak je slijedio Higuchijev model oslobađanja. Za vrijeme skladištenja na 45 C/75% RH nisu uočene nikakve značajne promjene u izgledu, sadržaju ljekovite tvari, sposobnosti plutanja i oslobađanju kaptoprila u in vitro uvjetima. Placebo pripravci s barijevim sulfatom u sloju za oslobađanje davani su volonterima. In vivo pokusi s rentgenskim zračenjem pokazali su da BFT pripravci imaju značajno produljeno vrijeme zadržavanja u želucu

A headspace-gas chromatography method for isopropanol determination in warfarin sodium products as a measure of drug crystallinity

Coumadin® and several generic products of warfarin sodium (WS) contain the crystalline form (clathrate) in which WS and isopropanol (IPA) are associated in a 2:1 molar ratio. IPA is critical in maintaining the WS crystalline structure. Physicochemical properties of the drug and drug product may change when the crystalline drug transforms to amorphous form. A headspace-gas chromatography (HS-GC) method was developed and validated for IPA determination in the WS drug product. n-propanol (NPA) was used as internal standard and the method was validated for specificity, system suitability, linearity, accuracy, precision, range, limits of detection and quantification, and robustness. The method was specific, with good resolution between IPA and NPA peaks. Chromatographic parameters (retention time, IPA/NPA area ratio, tailing factor, theoretical plates, USP symmetry, capacity factor, selectivity and resolution) were consistent over three days of validation. The analytical method was linear from 2–200 µg mL–1 (0.1–10 % IPA present in the drug product). LOD and LOQ were 0.1 and 2 µg mL–1, respectively. Accuracy at low (2 µg mL–1) and high (200 µg mL–1) IPA concentrations of the calibration curve was 103.3–113.3 and 98.9–102.2 % of the nominal value, resp. The validated method was precise, as indicated by the RSD value of less than 2 % at three concentration levels of the calibration curve. The method reported here was utilized to determine accurately and precisely the IPA content in in-house formulations and commercial products. In summary, IPA determination by HS-GC provides an indirect measure of WS crystallinity in the drug product. Nevertheless, it should be confirmed by another analytical method since IPA from the drug substance is not distinguishable from IPA that may be present outside the drug crystals in a dosage form when prepared by wet granulation with IPA

Ocular pharmacoscintigraphic and aqueous humoral drug availability of ganciclovir-loaded mucoadhesive nanoparticles in rabbits

The present report describes the improved ocular retention and aqueous humoral drug availability of ganciclovir (GCV) when administered via topical instillation of different kind of nanoparticles onto the rabbit eye. GCV was loaded into PLGA nanoparticles, chitosan-coated nanoparticles and chitosan-coated niosomal nanoparticles. All three formulations contained nanoparticles equally round in shape with a mean particle size in the range of 180–200 nm. The ocular corneal retention property was evaluated by gamma scintigraphy, revealing that the clearance was slowest in the case of the chitosan-containing formulations. GCV in chitosan-coated PLGA nanoparticles and chitosan-coated niosomal nanoparticles showed approx. 6-fold higher aqueous humor drug availability as compared to a GCV solution and nearly 2.5-fold higher as compared to the chitosan-lacking GCV-PLGA nanoparticles. The results indicate that the use of a mucoadhesive chitosan coating can improve the ocular residence time and aqueous humoral availability of GCV when administered topically in nanoparticle

Effect of drug-to-lipid ratio on nanodisc-based tenofovir drug delivery to the brain for HIV-1 infection

Background: Combination antiretroviral therapy has significantly advanced HIV-1 infection treatment. However, HIV-1 remains persistent in the brain; the inaccessibility of the blood–brain barrier allows for persistent HIV-1 infections and neuroinflammation. Nanotechnology-based drug carriers such as nanodiscoidal bicelles can provide a solution to combat this challenge. Methods: This study investigated the safety and extended release of a combination antiretroviral therapy drug (tenofovir)-loaded nanodiscs for HIV-1 treatment in the brain both in vitro and in vivo. Result: The nanodiscs entrapped the drug in their interior hydrophobic core and released the payload at the desired location and in a controlled release pattern. The study also included a comparative pharmacokinetic analysis of nanodisc formulations in in vitro and in vivo models. Conclusion: The study provides potential applications of nanodiscs for HIV-1 therapy development

Performance of RSMA-Based UOWC Systems Over Oceanic Turbulence Channel With Pointing Errors

Underwater optical wireless communication (UOWC) systems face significant challenges due to oceanic turbulence and pointing errors (PE), which can degrade system performance. Moreover, interference is another challenge in UOWC, considering the consistent increase in underwater optical devices. In this study, the performance of rate splitting multiple access (RSMA)-based UOWC systems is investigated over an exponential-generalized gamma (EGG)-distributed oceanic turbulence channel with generalized PE. The RSMA scheme is employed to facilitate communication between a source and multiple users in the UOWC system while accounting for the combined effects of oceanic turbulence and generalized PE. The statistical characterization of the UOWC system is analyzed, including the probability density function (PDF) of the signal-to-noise ratio (SNR), outage probability, throughput, and sum ergodic capacity. Additionally, closed-form expressions for the outage probability and throughput are derived, and asymptotic expressions for the outage probability in the high SNR regime are provided. Moreover, the diversity order of the system is evaluated, and the impact of different parameters on the system performance is discussed. Our results demonstrate the effectiveness of the RSMA-based UOWC system in mitigating the adverse effects of oceanic turbulence and PE while achieving improved performance in terms of capacity and outage probability. The findings of this study provide valuable insights for the design and optimization of UOWC systems in challenging underwater environments