This study aimed to develop a novel oral drug delivery system for gastroretentive sustained drug release by using a capsular device. A capsular device that can control drug release rates from the inner immediate release (IR) tablet while floating in the gastric fluid was fabricated and printed by a fused deposition modeling 3D printer. A commercial IR tablet of baclofen was inserted into the capsular device. The structure of the capsular device was optimized by applying a design of experiment approach to achieve sustained release of a drug while maintaining sufficient buoyancy. The 2-level factorial design was used to identify the optimal sustained release with three control factors: size, number, and height of drug-releasing holes of the capsular device. The drug delivery system was buoyant for more than 24 h and the average time to reach 80% dissolution (T₈₀) was 1.7–6.7 h by varying the control factors. The effects of the different control factors on the response factor, T₈₀, were predicted by using the equation of best fit. Finally, drug delivery systems with predetermined release rates were prepared with a mean prediction error ≤ 15.3%. This approach holds great promise to develop various controlled release drug delivery systems.

Ngo QT, et al. Nat Prod Sci. 2018 Jun;24(2):93-98. https://doi.org/10.20307/nps.2018.24.2.93

Docetaxel (DTX)-loaded polymeric micelles (DTBM) were formulated using the triblock copolymer, poly(ethylene glycol)–polylactide–poly(ethylene glycol) (PEG–PLA–PEG), to comprehensively study their pharmaceutical application as anticancer nanomedicine. DTBM showed a stable formulation of anticancer nanomedicine that could be reconstituted after lyophilization (DTBM-R) in the presence of PEG 2000 and D-mannitol (Man) as surfactant and protectant, respectively. DTBM-R showed a particle size less than 150 nm and greater than 90% of DTX recovery after reconstitution. The robustly formed micelles might minimize systemic toxicity due to their sustained drug release and also maximize antitumor efficacy through increased accumulation and release of DTX from the micelles. From the pharmaceutical development point of view, DTBM-R showing successful reconstitution could be considered as a potent nanomedicine for tumor treatment.

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox^®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC_0–48h of the commercial formulation, Sporanox^®, was 1073.9 ± 314.7 ng·h·mL⁻¹, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL⁻¹) was three-fold higher than that of Sporanox^® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC_0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL⁻¹ and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL⁻¹. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area.

The aim of this study was to prepare various types of solid dispersions (SDs) by the hot-melt extrusion technique. Next, process analytical technology (PAT) such as Fourier transform-infrared (FT-IR) and Raman and near infrared (NIR) spectroscopy were applied to determine the solubilization effect. The SDs and its tablets were prepared. SEM, DSC and XRD were performed to determine the morphological and crystalline characteristics of the SDs. Additionally, PAT analyses were performed to identify the solubilization of the celecoxib. Dissolution testing was performed using the paddle method indicated in the US Pharmacopeia Apparatus II. Based on SEM, DSC, and XRD analysis, all SDs changed successfully from the crystalline to the amorphous form. However, FT-IR, Raman, and NIR analysis used in PAT showed that SDs were divided into two groups. New peaks formed as the amount of drug loading increased to >50% in the SD, and the dissolution rates were lower than those of the marketed drug. Drug loading levels of ≤50% showed no new peak and exhibited strong solubilization effects. PAT tools can be used to discriminate between extrudates with poor (< 50% drug release after 120 min) and desirable (> 75% drug release after 120 min) dissolution performance.