Solid Dispersions of Gefitinib Prepared by Spray Drying with Improved Mucoadhesive and Drug Dissolution Properties

Gefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant (P < 0.05) increase in the ZD dissolution and release was observed from HPMC-based solid dispersion at pH 7.2 (up to 95% in 15 h), practically no drug was released at pH 1.2 and pH 6.5. Furthermore, the HPMC-based solid dispersions displayed enhanced mucoadhesive properties compared with PVP-based ones. Interestingly, cell viability studies using the neutral red assay showed that PVP and HPMC-based solid dispersions had no additional inhibitory effect on Caco-2 cell line compared to the pure drug.

Oral colon-targeting core–shell microparticles loading curcumin for enhanced ulcerative colitis alleviating efficacy

Background The oral colon-targeting drug delivery vehicle is vital for the efficient application of curcumin (Cur) in ulcerative colitis (UC) treatment because of its lipophilicity and instability in the gastrointestinal tract. Methods The core–shell microparticle (MP) system composed of eco-friendly materials, zein and shellac, was fabricated using a coaxial electrospray technique. In this manner, Cur was loaded in the zein core, with shellac shell coating on it. The colon-targeting efficiency and accumulation capacity of shellac@Cur/zein MPs were evaluated using a fluorescence imaging test. The treatment effects of free Cur, Cur/zein MPs, and shellac@Cur/zein MPs in acute experimental colitis were compared. Results With the process parameters optimized, shellac@Cur/zein MPs were facilely fabricated with a stable cone-jet mode, exhibiting standard spherical shape, uniform size distribution (2.84 ± 0.15 µm), and high encapsulation efficiency (95.97% ± 3.51%). Particularly, with the protection of shellac@zein MPs, Cur exhibited sustained drug release in the simulated gastrointestinal tract. Additionally, the in vivo fluorescence imaging test indicated that the cargo loaded in shellac@zein MPs improves the colon-targeting efficiency and accumulation capacity at the colonitis site. More importantly, compared with either free Cur or Cur/zein MPs, the continuous oral administration of shellac@Cur/zein MPs for a week could efficiently inhibit inflammation in acute experimental colitis. Conclusion The shellac@Cur/zein MPs would act as an effective oral drug delivery system for UC management.

Response surface method for optimization of prepared satranidazole powder layered pellets

Background The purpose of the present study was to evaluate layered of satranidazole powder using natural polysaccharides as coating materials for colon targeting that were inexpensive and natural with a non-toxic nature using a composite response design of 3 levels and 2 factors for each of the four responses in the quadratic model. The independent variables were the ratio of coating consistency % (X1) and coating level % (X2) in the pellet. The dependent factors were % release of drug at 2 h. (Y1), % release of drug at 6 h. (Y2), % release of drug difference in presence & absence of colonic enzyme (Y3) and mean dissolution time (Y4). The various models were fitted for the responses with an explanation of suitable statistical methods. Variance analysis and different factor levels of responses were constructed by response surface plots. Results Satranidazole pellets were efficiently prepared by the variable amount of ingredients that showed compatibility with possible pellet characterization and drug dissolution profiles to optimize the formulation. Conclusions The strategy of response surface can be a successful tool for improving the prepared satranidazole pellets which can be an appropriate replacement of regular one.

The Chronotopic™ System for Pulsatile and Colonic Delivery of Active Molecules in the Era of Precision Medicine: Feasibility by 3D Printing via Fused Deposition Modeling (FDM)

The pulsatile-release Chronotopic™ system was conceived of as a drug-containing core surrounded by a coat made of swellable/soluble hydrophilic polymers, the latter being able to provide a programmable lag phase prior to drug liberation. This system was also proposed in a colon-targeting configuration, entailing a gastroresistant film to prevent early interaction of the inner coat with gastric fluids and enabling the attainment of a lag phase matching the small intestinal transit time. Over the years, various multiple-step manufacturing processes have been tested for the fabrication of the Chronotopic™ system in both its configurations. This work focused on the evaluation of 3D printing by fused deposition modeling in view of its potential towards product personalization, on demand one-step manufacturing and efficient scale down of batches. The feasibility of each part of the Chronotopic™ system was independently investigated starting from in-house made filaments, characterizing the resulting specimens for physico-technological and performance characteristics. The printing parameters identified as suitable during the set-up phase were then used to fabricate prototypes either in a single step for the pulsatile configuration or following two different fabrication approaches for the colon-targeting one.