Viability of Lactobacillus acidophilus in Thin-Film Freeze-Dried Powders Filled in Delayed-Release Vegetarian Capsules in a Simulated Gastric Fluid.

Previously, we have shown that thin-film freeze-drying can be applied to prepare dry powders of bacteria such as Lactobacillus acidophilus. Herein, we tested the viability of L. acidophilus in thin-film freeze-dried powders (TFF powders) filled in delayed-release vegetarian capsules in a simulated gastric fluid (SGF) consisting of 0.1N hydrochloric acid and sodium chloride. Initially, we determined the water removal rate from frozen thin films on relatively larger scales (i.e., 10-750 g). We then prepared and characterized two TFF powders of L. acidophilus with either sucrose and maltodextrin or sucrose and hydroxypropyl methylcellulose acetate succinate (HPMC-AS), a pH-sensitive polymer, as excipients and evaluated the viability of the bacteria after the TFF powders were filled in delayed-release vegetarian capsules and the capsules were incubated in the SGF for 30 min. On 10-750 g scales and at the settings specified, water removal from frozen thin films was faster than from slow shelf-frozen bulk solids. When the L. acidophilus in sucrose and HPMC-AS TFF powder was filled into a delayed-release capsule that was placed into another delayed-release capsule, the bacterial viability reduction after incubation in the SGF can be minimized to within 1 log in colony forming unit (CFU). However, for the L. acidophilus in sucrose and maltodextrin TFF powder, even in the capsule-in-capsule dosage form, bacterial CFU reduction was > 2 logs. TFF powders of live microorganisms containing an acid-resistant material in capsule-in-capsule delayed-release vegetarian capsules have the potential for oral delivery of those microorganisms.

Comparison of HPMC Inhalation-Grade Capsules and Their Effect on Aerosol Performance Using Budesonide and Rifampicin DPI Formulations.

Despite the fact that capsules play an important role in many dry powder inhalation (DPI) systems, few studies have been conducted to investigate the capsules' interactions with respirable powders. The effect of four commercially available hydroxypropyl methylcellulose (HPMC)inhalation-grade capsule types on the aerosol performance of two model DPI formulations (lactose carrier and a carrier-free formulation) at two different pressure drops was investigated in this study. There were no statistically significant differences in performance between capsules by using the carrier-based formulation. However, there were some differences between the capsules used for the carrier-free rifampicin formulation. At 2-kPa pressure drop conditions, Embocaps® VG capsules had a higher mean emitted fraction (EF) (89.86%) and a lower mean mass median aerodynamic diameter (MMAD) (4.19 µm) than Vcaps® (Capsugel) (85.54%, 5.10 µm) and Quali-V® I (Qualicaps) (85.01%, 5.09 µm), but no significant performance differences between Embocaps® and ACGcaps™ HI. Moreover, Embocaps® VG capsules exhibited a higher mean respirable fraction (RF)/fine particle fraction (FPF) with a 3-µm-sized cutoff (RF/FPF< 3 µm) (33.05%/35.36%) against Quali-V® I (28.16%/31.75%) (P < 0.05), and a higher RF/FPF with a 5-µm-sized cutoff (RF/FPF< 5 µm) (49.15%/52.57%) versus ACGcaps™ HI (38.88%/41.99%) (P < 0.01) at 4-kPa pressure drop condition. Aerosol performance variability, pierced-flap detachment, as well as capsule hardness and stiffness, may all influence capsule type selection in a carrier-based formulation. The capsule type influenced EF, RF, FPF, and MMAD in the carrier-free formulation.

A Quality by Design Framework for Capsule-Based Dry Powder Inhalers.

Capsule-based dry powder inhalers (cDPIs) are widely utilized in the delivery of pharmaceutical powders to the lungs. In these systems, the fundamental nature of the interactions between the drug/formulation powder, the capsules, the inhaler device, and the patient must be fully elucidated in order to develop robust manufacturing procedures and provide reproducible lung deposition of the drug payload. Though many commercially available DPIs utilize a capsule-based dose metering system, an in-depth analysis of the critical factors associated with the use of the capsule component has not yet been performed. This review is intended to provide information on critical factors to be considered for the application of a quality by design (QbD) approach for cDPI development. The quality target product profile (QTPP) defines the critical quality attributes (CQAs) which need to be understood to define the critical material attributes (CMA) and critical process parameters (CPP) for cDPI development as well as manufacturing and control.