Current Issue : October-December Volume : 2023 Issue Number : 4 Articles : 5 Articles
An extended-release tablet of tacrolimus as once-daily dosing was fabricated using 3D printing technology. It was developed by combining two 3D-printing methods in parallel. Indeed, an optimized mixture of PVA, sorbitol, and magnesium stearate as a shell compartment was printed through a hot-melt extrusion (HME) nozzle while an HPMC gel mixture of the drug in the core compartment was printed by a pressure-assisted micro-syringe (PAM). A 3D-printed tablet with an infill of 90% was selected as an optimized formula upon the desired dissolution profile, releasing 86% of the drug at 12 h, similar to the commercial one. The weight variation, friability, hardness, assay, and content uniformity determination met USP requirements. A microbial evaluation showed that the 3D-printed tablet does not support microbial growth. SEM analysis showed smooth surfaces with multiple deposited layers. No peak interference appeared based on FTIR analysis. No decomposition of the polymer and drug was observed in the printing temperature, and no change in tacrolimus crystallinity was detected based on TGA and DSC analyses, respectively. The novel, sTable 3D-printed tablet, fabricated using controllable additive manufacturing, can quickly provide tailored dosing with specific kinetic release for personalized medicine at the point-of-care....
This study aimed to develop a biopredictive dissolution method for desvenlafaxine ER tablets using design of experiments (DoE) and physiologically based biopharmaceutics modeling (PBBM) to address the challenge of developing generic drug products by reducing the risk of product failure in pivotal bioequivalence studies. For this purpose, a PBBM was developed in GastroPlus® and combined with a Taguchi L9 design, to evaluate the impact of different drug products (Reference, Generic #1 and Generic #2) and dissolution test conditions on desvenlafaxine release. The influence of the superficial area/volume ratio (SA/V) of the tablets was observed, mainly for Generic #1, which presented higher SA/V than the others, and a high amount of drug dissolved under similar test conditions. The dissolution test conditions of 900 mL of 0.9% NaCl and paddle at 50 rpm with sinker showed to be biopredictive, as it was possible to demonstrate virtual bioequivalence for all products, despite their release-pattern differences, including Generic #3 as an external validation. This approach led to a rational development of a biopredictive dissolution method for desvenlafaxine ER tablets, providing knowledge that may help the process of drug product and dissolution method development....
In this work, film materials based on binary compositions of poly-(3-hydroxybutyrate) (PHB) and chitosan with different ratios of polymer components in the range from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the influence of the encapsulation temperature of the drug substance (DS) of dipyridamole (DPD) and moderately hot water (at 70 ◦C) on the characteristics of the PHB crystal structure and the diffusion rotational mobility of the stable TEMPO radical in the amorphous regions of the PHB/chitosan compositions is shown. The low-temperature extended maximum on the DSC endotherms made it possible to obtain additional information about the state of the chitosan hydrogen bond network. This allowed us to determine the enthalpies of thermal destruction of these bonds. In addition, it is shown that when PHB and chitosan are mixed, significant changes are observed in the degree of crystallinity of PHB, degree of destruction of hydrogen bonds in chitosan, segmental mobility, sorption capacity of the radical, and the activation energy of rotational diffusion in the amorphous regions of the PHB/chitosan composition. The characteristic point of polymer compositions was found to correspond to the ratio of the components of the mixture 50/50%, for which the inversion transition of PHB from dispersed material to dispersion medium is assumed. Encapsulation of DPD in the composition leads to higher crystallinity and to a decrease in the enthalpy of hydrogen bond breaking, and it also slows down segmental mobility. Exposure to an aqueous medium at 70 ◦C is also accompanied by sharp changes in the concentration of hydrogen bonds in chitosan, the degree of PHB crystallinity, and molecular dynamics. The conducted research made it possible for the first time to conduct a comprehensive analysis of the mechanism of action of a number of aggressive external factors (such as temperature, water, and the introduced additive in the form of a drug) on the structural and dynamic characteristics of the PHB/chitosan film material at the molecular level. These film materials have the potential to serve as a therapeutic system for controlled drug delivery....
Linalool is an aromatic oil with analgesic, anti-inflammatory and anti-UVB-induced skin damage effects. The aim of this study was to develop a linalool-loaded microemulsion formulation for topical application. In order to quickly obtain an optimal drug-loaded formulation, statistical tools of the response surface methodology and a mixed experimental design with four independent variables of oil (X1), mixed surfactant (X2), cosurfactant (X3) and water (X4) were used to design a series of model formulations in order to analyze the effect of the composition on the characteristics and permeation capacity of linalool-loaded microemulsion formulations and to obtain an appropriate drug-loaded formulation. The results showed that the droplet size, viscosity and penetration capacity of linalool-loaded formulations were significantly affected by formulation component proportions. The skin deposition amount of the drug and flux of such formulations expressively increased about 6.1-fold and 6.5-fold, respectively, when compared to the control group (5% linalool dissolved in ethanol). After 3 months of storage, the physicochemical characteristics and drug level did not show a significant change. The linalool formulation-treated rat skin showed non-significant irritation compared to skin treatments in the distilled-water-treated group. The results showed that specific microemulsion applications might be considered as potential drug delivery carriers for essential oil topical application....
Mycobacterium tuberculosis (M.tb) has infected one-quarter of the world’s population and led to the deaths of 1.6 million individuals in 2021 according to estimates from the World Health Organization. The rise in prevalence of multidrug-resistant and extensively drug-resistant M.tb strains coupled with insufficient therapies to treat such strains has motivated the development of more effective treatments and/or delivery modalities. Bedaquiline, a diarylquinoline antimycobacterial agent, effectively targets mycobacterial ATP synthase but may lead to systemic complications upon oral delivery. Targeted delivery of bedaquiline to the lungs represents an alternative strategy to harness the sterilizing benefits of the drug against M.tb while mitigating off-target side effects. Two pulmonary delivery modalities were developed herein, including dry powder inhalation and liquid instillation. Despite bedaquiline’s poor water solubility, spray drying was performed in predominantly aqueous conditions (≥80%) to avoid a closed-loop, inert system. Aerosols of spray-dried bedaquiline with L-leucine excipient outperformed spray-dried bedaquiline alone, demonstrating superior fine particle fraction metrics (~89% of the emitted dose below <5 μm), suitable for inhalation therapies. Furthermore, the use of a 2-hydroxypropyl-β-cyclodextrin excipient allowed a molecular dispersion of bedaquiline in an aqueous solution for liquid instillation. Both delivery modalities were successfully administered to Hartley guinea pigs for pharmacokinetic analysis and were welltolerated by the animals. Intrapulmonary liquid delivery of bedaquiline led to adequate serum absorption and appropriate peak serum concentrations of the drug. The liquid formulation was superior in systemic uptake compared to the powder formulation. The predominant route via which M.tb bacilli enter the body is aerosol droplets that are deposited onto airway surfaces. For this reason, we believe that further studies should focus on inhalation or intrapulmonary therapies that target the site of entry and primary site of infection for M.tb....
Loading....