Formulation Development and Evaluation of Multiple Unit Pellet System of Tamsulosin Hydrochloride

The aim of current work was to grow extended release multiple unit pellets of Tamsulosin Hydrochloride, is an alpha-blocker, used for the healing of the symptoms of a prostate gland condition called BPH (benign prostatic hyperplasia) by extrusion- spheronization (E/S) and solution/suspension layering (S/S) method. In the Extrusion-Spheronization, A ratio of 75:25, 67:33, 64:36 Tamsulosin Hydrochloride and Microcrystalline cellulose were mixed for making drug pellets and extended release (ER) coating was performed in fluidized bed processor (FBP) by solution/suspension layering with Ethyl cellulose (aqueous. dispersion, 4 cps and 7 cps) and Hypromellose (5cps) with different ratios % weight buildups accordingly. In the Solution/suspension layering (S/S) method, Tamsulosin Hydrochloride drug pellets were prepared by layering onto MCC spheres in FBP. These drug pellets were further coated for extended release with HPMC, 5cps and EC, 7cps. In drug coating stage, drug and different binder (Hypromellose, 5 cps) concentrations 8, 10, 12, 14 mg/unit were coated onto the cores for optimization of binder concentration. The weight of MCC spheres were optimized for further formulations. For all the drug coated pellets, ER coating was given with EC, 7cps and HPMC, 5 cps at a coating level of 8% weight by weight. In the extrusion- spheronization (E/S) Optimization of Drug pellets: Among the trials TD3 (Tamsulosin HCl and MCC) showed good mechanical strength with better yield due to increased MCC concentration. Optimization of Extended Release Coating: Optimized TD3 drug pellets were coated with ER coating using water insoluble polymer (Aq.EC 25% dispersion/ EC, 4cps/ EC, 7cps) and water soluble polymer (HPMC, 5cps). Among these polymers, extended release coating was optimized (TD3E14) with the combination of EC, 7cps and HPMC, 5cps at 8% weight build up. In the Solution/Suspension layering: Optimization of binder concentration in drug coating stage: HPMC, 5cps with 12 mg/unit for TF7 was optimized based on %yield. Optimization of MCC spheres in drug coating stage in formulation of ER pellets with different weight drug pellets: The weight of MCC spheres (160, 170, 180, 190 mg/unit) used in the drug coating stage with binder HPMC, 5cps (12 mg/unit). These drug pellets were given with ER coating at 8% weight buildup by using EC, 7cps and HPMC, 5cps. Among these trials, TF7E7 was optimized. Based on the investigations of the present study, conclusions was. formulating low dose, high soluble, BCS class I drug- Tamsulosin Hydrochloride ER formulation by extrusion-spheronization showed flexibility for batch processing and cost effectiveness while solution/suspension layering was process feasible but time consuming due to high drug loading.

pH-driven enhancement of anti-tubercular drug loading on iron oxide nanoparticles for drug delivery in macrophages

Nanoparticle deployment in drug delivery is contingent upon controlled drug loading and a desired release profile, with simultaneous biocompatibility and cellular targeting. Iron oxide nanoparticles (IONPs), being biocompatible, are used as drug carriers. However, to prevent aggregation of bare IONPs, they are coated with stabilizing agents. We hypothesize that, zwitterionic drugs like norfloxacin (NOR, a fluoroquinolone) can manifest dual functionality – nanoparticle stabilization and antibiotic activity, eliminating the need of a separate stabilizing agent. Since these drugs have different charges, depending on the surrounding pH, drug loading enhancement could be pH dependent. Hence, upon synthesizing IONPs, they were coated with NOR, either at pH 5 (predominantly as cationic, NOR+) or at pH 10 (predominantly as anionic, NOR−). We observed that, drug loading at pH 5 exceeded that at pH 10 by 4.7–5.7 times. Furthermore, only the former (pH 5 system) exhibited a desirable slower drug release profile, compared to the free drug. NOR-coated IONPs also enable a 22 times higher drug accumulation in macrophages, compared to identical extracellular concentrations of the free drug. Thus, lowering the drug coating pH to 5 imparts multiple benefits – improved IONP stability, enhanced drug coating, higher drug uptake in macrophages at reduced toxicity and slower drug release.

Results of long-term patency of small-diameter biodegradable vascular prostheses with atrombogenic drug coating of sheep model

Background. Preclinical tests of biodegradable small diameter vascular prostheses on a sheep model have been carried out.Aim. To assess the results of long-term patency and remodeling of biodegradable vascular prostheses based on polyhydroxybutyrate / valerate and polycaprolactone with an atrombogenic drug coating in a large laboratory animal model.Methods. We researched vascular prostheses made of polyhydroxybutyrate / valerate and polycaprolactone (PHBV/PCL) 4 mm in diameter with layer-by-layer vascular endothelial growth factor incorporated into the polymer framework, the main fibroblast growth factor, chemoattractant molecule containing SDF-1a (GFmix) surface, and additional modifying drug surface heparin and iloprost (PHBV/PCL/ GFmix/Heparin/Iloprost). Animals with implanted synthetic Gore-Tex vascular grafts with a diameter of 4 mm were included into a comparison group.Results. After one day of implantation it was revealed that the patency of biodegradable PHBV/PCL/GFmix/Heparin/Iloprost prostheses was 62.5%, while synthetic Gore-Tex prostheses were thrombosed in 100% of cases. At the same time, after 18 months of implantation, the patency of biodegradable vascular PHBV/PCL/ GFmix/Heparin/Iloprost prostheses decreased to 50%. Passable drug-eluting polymer grafts were completely resorbed after 18 months of implantation, and aneurysmically expanded newly formed vascular tissue was formed in their place.Conclusion. Vascular prostheses made of polyhydroxybutyrate/valerate and polycaprolactone showed better long-term patency results than synthetic prostheses used in the clinical practice. However, the strengthening of the external framework of the prostheses is required in order to prevent the formation of aneurysms.

Evaluation of the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer composition with atrombogenic and antimicrobial drug coating

Creation of vascular grafts with atrombogenic and antimicrobial coating is a very important area.Objective: to evaluate the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer compositions with atrombogenic and antimicrobial drug coating.Materials and methods. Modification of the surface of the biodegradable vascular grafts was performed through complexation with polyvinylpyrrolidone, which was polymerized with polymer scaffold surface by means of ionizing radiation at 10 and 15 kGy. Physical and mechanical properties, as well as hemocompatibility were evaluated. Bacteriological studies were carried out using test strains of gram-negative and gram-positive microorganisms: Klebsiella pneumoniae spp. ozaena No. 5055, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Proteus mirabillis ATCC3177, Pseudomonas aeruginosa.Results. There was no influence of modifying manipulations with ionizing radiation on the physical and mechanical characteristics of biodegradable prostheses. Vascular grafts with atrombogenic and antimicrobial coatings exhibited atrombogenic properties upon contact with blood, reducing platelet aggregation by 5–7 times (p < 0.05). Also decrease in adhesion and platelets deformation index was found on the surface of drug-eluting scaffolds (for PCL-based prostheses, the latter decreased by 1.9 times relative to unmodified counterparts (p < 0.05), for PHBV/PCL-based prostheses – by 1.3 times relative to unmodified counterparts and 1.5 times relative to scaffolds with polyvinylpyrrolidone (p < 0.05). Bacteriological studies revealed a local inhibitory effect in the place where scaffolds with cationic amphiphile were applied on agar. No growth retardation zones were identified. Polymeric composition of the scaffolds and the used dose of ionizing radiation did not lead to a difference in the bacteriostatic properties of the scaffolds with amphiphile.Conclusion. A full cycle of surface modification of biodegradable polymer prostheses based on both PCL and РHBV/PCL composition resulted in significant increase in the atrombogenic and antimicrobial properties of prostheses and did not worsen the physical-mechanical and biocompatible properties of the structures being developed.

PDLLA-Zn-nitrided Fe bioresorbable scaffold with 53-μm-thick metallic struts and tunable multistage biodegradation function

Balancing the biodegradability and mechanical integrity of a bioresorbable scaffold (BRS) with time after implantation to match the remodeling of the scaffolded blood vessel is important, but a key challenge in doing so remains. This study presents a novel intercalated structure of a metallic BRS by introducing a nanoscale Zn sacrificial layer between the nitrided Fe platform and the sirolimus-carrying poly(d,l-lactide) drug coating. The PDLLA-Zn-FeN BRS shows a multistage biodegradation behavior, maintaining mechanical integrity at the initial stage and exhibiting accelerated biodegradation at the subsequent stage in both rabbit abdominal aortas and human coronary arteries, where complete biodegradation was observed about 2 years after implantation. The presence of the nanoscale Zn sacrificial layer with an adjustable thickness also contributes to the tunable biodegradation of BRS and allows the reduction of the metallic strut thickness to 53 μm, with radial strength as strong as that of the current permanent drug-eluting stents.

Application of Gibbs Sampling in Modelling the Utilization Rate of Raw Materials for Drug Coating

Drug coating is one of the most important processes in the modern pharmaceutical industry. Improving the utilization rate of raw materials (URRM) in the drug coating process is thus important for cost saving and efficiency enhancement. There is little existing research on this topic in the literature of applied statistics. In this paper, motivated by a real dataset collected from a pharmaceutical company in China, we propose to use a novel predictive model that integrates a Bayesian framework with the Gibbs sampling algorithm to characterize the pattern of URRM. Based on certain prior distributional assumptions, the Gibbs sampling algorithm is then applied to sample the posterior distribution of the parameters to obtain more accurate and robust estimation results. By using the proposed method, the drugs can be properly separated into several categories with different patterns of URRM, and the pattern of each category can be properly recognized with selected covariates, which achieves the goals of clustering, variable selection, and regression simultaneously, and provides valuable insights into the improvement of the URRM for drug coating. Numerical studies show that the proposed method works well in practice.