Benchmarking pharmaceutical quality and manufacturing costs of 3D printing against conventional compounding methods for personalization of medicine

Background: Modification of commercially available medicine, e.g. splitting or dissolving of tablets or pharmacy compounding, is current clinical practice when desired oral dosage forms are unavailable. These practices are defined as conventional pharmacy compounding techniques and are used to produce medicines that are not commercially available. 3D printing is an automated compounding technique that allows pharmacists to personalize oral dosage forms. This study aimed to compare the quality of 3D printing hydrocortisone tablets with conventional pharmacy compounded formulations. Secondary and tertiary aims were to assess manufacturing costs of 3D printed tablets and to explore whether modifying the hydrocortisone drug release profile is possible using 3D printing. Methods: Semi-solid extrusion (SSE) 3D printing was used to produce immediate release and sustained release hydrocortisone tablets. Conventional compounded hydrocortisone formulations were used as comparators, including pharmacy compounded capsules, split tablets, and commercially available tablets dissolved in syringes. Results: Immediate and sustained release hydrocortisone tablets were printed successfully. The acceptance values (AVs) of 3D printed tablets, tablet dissolved-in-syringe and one batch of pharmacy compounded capsules were ≤ 15. The AVs of the other 2 pharmacy compounded capsules and split tablets were &gt; 15 and did not comply with content uniformity requirements. Personalization of 3D printed tablets was possible with a dose range of 0.5 – 10.0 mg. Costs of 3D printed tablets were &lt;€ 3.00 per tablet for both release profiles. Conclusion: SSE 3D printing leads to higher quality hydrocortisone tablets compared to conventional pharmacy compounding methods at acceptable manufacturing costs. 3D printing further allows for modification of hydrocortisone release profiles, which is not possible using conventional manufacturing methods. The low dose minitablets are especially suitable for pediatric indications requiring a personalized hydrocortisone dose.</p

Aerosolized Delivery of Antifungal Agents

Pulmonary infections caused by Aspergillus species are associated with significant morbidity and mortality in immunocompromised patients. Although the treatment of pulmonary fungal infections requires the use of systemic agents, aerosolized delivery is an attractive option in prevention because the drug can concentrate locally at the site of infection with minimal systemic exposure. Current clinical evidence for the use of aerosolized delivery in preventing fungal infections is limited to amphotericin B products, although itraconazole, voriconazole, and caspofungin are under investigation. Based on conflicting results from clinical trials that evaluated various amphotericin B formulations, the routine use of aerosolized delivery cannot be recommended. Further research with well-designed clinical trials is necessary to elucidate the therapeutic role and risks associated with aerosolized delivery of antifungal agents. This article provides an overview of aerosolized delivery systems, the intrapulmonary pharmacokinetic properties of aerosolized antifungal agents, and key findings from clinical studies

Liposomal budesonide for dry powder inhaler: Preparation and stabilization

The purpose of the study was to prepare stable liposomally entrapped budesonide (BUD) for a dry powder inhaler (DPI) formulation. BUD liposomes composed of egg phosphatidyl choline and cholesterol were prepared by lipid film hydration technique and sonicated to have the desired size (<5 μm). A rapid method was used for separation of free drug by centrifugation at a lower centrifugal force (G value). Liposomal dispersion was subjected to lyophilization after blending BUD with cryoprotectant in varying bulk and mass ratios, and percent drug remaining entrapped after lyophilization was optimized. Comparative drug retention studies on storage of DPI formulations were carried out in accordance with International Conference on Harmonization guidelines. Critical relative humidity of the formulations was determined and reported as one of the manufacturing controls. Sucrose was found to be the most effective cryoprotectant when present on both sides of the lamellae of liposomes in a bulk strength of 500 mM and mass ratio of lipid:sugar; 1∶10. Blending of sorbolac before lyophilization showed better retention of encapsulated drug (95.59%). The respirable fraction of the product (20.69±1.50%) was comparable with that of the control (26.49±1.52%), suggesting that the liposomal BUD can be successfully delivered throughout the broncho-pulmonary tree. The findings demonstrate that liposome of BUD can be prepared with a high entrapment value, stabilized by lyophilization, and delivered as an aerosolized DPI. The stability studies of lyophilized product suggests a shelf-life of one year when stored under refrigeration (2°C–8°C)