Current Issue : October-December Volume : 2025 Issue Number : 4 Articles : 5 Articles
Background/Objectives: Hospital compounding is essential for the delivery of patienttailored therapies—particularly for pediatric and oncology patients and other groups requiring precise dosing. Its role is expected to grow as, for instance, the UK MHRA’s new Guidance on Decentralised Manufacturing promotes alternative manufacturing pathways that integrate hospital preparation units. However, drug substances that remain stable in commercial oral formulations may undergo rapid degradation under alternative conditions (e.g., aqueous suspension, light exposure, or in the presence of specific excipients). Despite these risks, formulation strategies in hospital compounding often rely on empirical practices and lack structured guidance regarding stability, impurity control, and reproducibility. Methods: This study proposes a risk-based scientific framework for formulation design, integrating degradation profiling with predictive toxicology. Potential degradation pathways (hydrolytic, oxidative, and photolytic) are systematically identified through forced-degradation studies combined with ab initio modeling. These risks are translated into formulation strategies using a structured decision tree encompassing solvent selection, pH adjustment, excipient compatibility, and packaging considerations, even in the absence of a pharmacopeial monograph. The toxicological relevance of degradation products is evaluated using in silico approaches aligned with ICH M7 guidelines, thereby defining critical quality attributes (cQAs) and critical process parameters (CPPs). Results: The applicability of the framework is demonstrated through hospital compounding case studies, with further extension toward advanced applications such as semi-solid extrusion (SSE) 3D printing. Conclusions: By integrating mechanistic understanding of drug degradation into formulation planning, the proposed framework enhances the safety, reproducibility, and quality of compounded preparations. This approach reinforces Good Preparation Practices (GPPs) and is consistent with international quality-by-design (QbD) principles in the context of personalized medicine....
Background/Objectives: Glaucoma is the leading cause of irreversible blindness worldwide and oxidative stress is considered to play a key role in its development. While antioxidants offer a promising approach to mitigating oxidative stress, their clinical application is often hindered by bioavailability and absorption challenges. Entrapment antioxidants within liposomes may overcome these issues, enhancing their stability and delivery. The aim of this study was to develop a novel composite liposomal formulation for glaucoma treatment, designed to enhance lipoic acid bioavailability and administration through its incorporation into the lipid bilayer. Methods: Liposomes were prepared via lipid film hydration and extrusion. To characterize them, the following analyses were performed: FTIR spectroscopy, liposomal bilayer melting temperature (Tm), TEM, DLS, Zpotential, antioxidant activity, and cytotoxicity assays. Results: The efficient incorporation of lipoic acid into the liposomes’ lipid bilayer was confirmed by FTIR. This incorporation resulted in an increase in the Tm, from 37.0 ◦C for liposomes to 40.0 ◦C for liposomes with lipoic acid (L-LA). TEM images confirmed that the spherical morphology of the lipid vesicles remained unchanged following LA incorporation. Dynamic Light Scattering analysis revealed effective diameters of 423 ± 36 nm for L liposomes and 404 ± 62 nm for L-LA liposomes. Notably, the Z-potential shifted from +4.7 ± 0.4 mV (L) to −0.4 ± 0.3 mV (L-LA). Furthermore, L-LA exhibited significant antioxidant activity (31.6 ± 0.4%) compared with L (5.3 ± 0.3%) and biocompatibility, suggesting its potential for therapeutic applications. Conclusions: In summary, biocompatible composite liposomes with antioxidant capacity were successfully developed, resulting in promising candidates for neuroprotective glaucoma therapy....
Methods: Effervescent granules containing citric acid and sodium bicarbonate were successfully prepared for the first time via TS-MG using a polyol (sorbitol) as a melt binder. Results: Processing parameters, specifically granulation temperature and screw speed, were systematically varied to investigate their influence. The granulation efficiency, inversely related to the wt.% of fines, decreased in the following order across the tested conditions (granulation temperature–screw speed; °C-rpm): 95-6 > 100-5 > 90-5 > 100-7 > 90-7. Granulation temperature had a minimal impact on the bulk and tapped densities of the uncalibrated granules, whereas increased screw speed led to higher densities, associated with a reduced proportion of fines. The tensile strength of the resulting effervescent tablets increased with granulation temperature and was generally higher for tablets derived from granules with higher granulation efficiency. The residence time within the TS-MG barrel decreased with increasing temperature and screw speed. Notably, the greatest effect of granulation temperature on tensile strength occurred between 90 and 95 ◦C, particularly under longer residence times. The disintegration time of the tablets was shortest for the 90 ◦C and 5 rpm condition, corresponding to the lowest tensile strength, while tablets across formulations showed consistent homogeneity as indicated by similar pH values post-disintegration. Conclusions: These findings underscore sorbitol’s suitability as a melt binder and highlight the interplay between TS-MG parameters and the physical characteristics of effervescent granules and tablets....
Abstract: Background/Objectives: This study aimed to evaluate the degradation of omeprazole suspension under various pH conditions and to propose recommendations for preparing compounded suspensions. Given the clinical need for alternative dosage forms for pediatric and geriatric patients and those with dysphagia, the research focused on assessing whether modifications in formulation composition—specifically the inclusion of sodium bicarbonate—could improve omeprazole stability, thus enhancing its bioavailability. Methods: Three formulations were prepared: O1, based on crushed enteric-coated pellets from a commercial product; O2, with crushed pellets suspended in an 8% sodium bicarbonate solution with glycerin; and O3, with pure omeprazole suspended in an 8% sodium bicarbonate solution with glycerin. Release studies were conducted using basket or paddle apparatus under conditions simulating fasted (pH 1.2 and 6.8) and fed (pH 6, 4.5, and 3) gastric and intestinal juices at 37 ◦C over 120 min. At predetermined intervals, samples were withdrawn and analyzed by a validated HPLC method with UV detection to quantify the released omeprazole. Results: The commercial enteric-coated product showed no release at a low pH, confirming its protective coating. In contrast, formulation exhibited significant degradation in acidic environments. The O2 formulation, benefiting from the buffering effect of sodium bicarbonate, showed improved stability compared to O1. Notably, formulation O3 yielded the highest drug recovery, with approximately 74% released at pH 6 and 65% at pH 6.8, demonstrating significantly better performance, as confirmed by statistical analysis (p < 0.05). Conclusions: The composition of omeprazole suspensions substantially influences the drug stability and release profiles. The O3 formulation, based on pure omeprazole with sodium bicarbonate, is recommended for immediate-release suspensions to enhance bioavailability. Further studies are needed to optimize conditions for pediatric use....
Background: Physiologically based biopharmaceutics modeling (PBBM) models can help to predict drug release and in vivo absorption behaviors. Colon drug delivery systems have gained interest over the past few years due to the advantages they provide in treating certain diseases in a local way. The objectives of this work were to simulate the biopharmaceutical and pharmacokinetic behavior of metronidazole hydrophilic matrices coated with different enteric polymers and to highlight the factors with a significant impact on the simulated pharmacokinetic parameters. Methods: Physicochemical properties of metronidazole were introduced into Simcyp® simulator platform, and the Advanced Dissolution Absorption Model (ADAM) was employed to simulate the in vivo intestinal absorption and colonic concentrations of metronidazole using a PBBM model. A Kruskal– Wallis test was carried out in order to determine which one of the factors studied has a statistically significant impact on the pharmacokinetic parameters (AUC, Cmax, and Tmax) simulated. Results: Enteric-coated matrix tablets are capable of avoiding metronidazole absorption in the small intestine and releasing it in the colonic region. The release and absorption rates of metronidazole depend largely on the percentage of weight gain of the coating and also on the coating agent. Coated tablets with a time-dependent coating show less variability. Conclusions: PBBM models can help predict the release from drug delivery systems and the pharmacokinetics in vivo of metronidazole from data obtained in vitro, although complementary in vivo studies should be needed....
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