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.

Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device

Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler® and the high resistance Handihaler® as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler® and the Handihaler®. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 ± 0.67% w/w and particle mass median aerodynamic diameters of down to 1.90 ± 0.20 μm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 ± 3.46% w/w and particle mass median aerodynamic diameters of down to 6.79 ± 0.82 μm. When leucine was used as an excipient, using 50% w/w rather than 25% w/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w/w (95% confidence interval = 6.40–12.73% w/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler® outperformed the Handihaler® as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w/w (95% confidence interval = 8.17–10.16% w/w).

Increasing the Yield of Powder and Bioactive Materials during Extraction and Spray Drying of Dragon Fruit Skin Extracts

One potential utilization of dragon fruit skin is to produce bioactive materials as natural antioxidants and colorants for the food industry by extraction and spray drying. This study investigated the quality (total phenolic compounds/TPC, betacyanin and betaxanthin contents, and antioxidant activity) of the extracts and spray-dried products, and the quantity (powder yield) obtained by the use of different types and amounts of spray drying agents. Two drying agents were introduced during spray drying, i.e. maltodextrin and whey protein isolate (WPI). The result showed that a lower extraction solvent to solid ratio may result in a lower yield of TPC, betacyanin and betaxanthin contents, and also in antioxidant activity of the dragon fruit skin extract. In addition, maltodextrin and WPI were found to be able to significantly increase the yield from spray drying. The highest yield (72.7 ± 8.4%) was obtained with the use of 40% maltodextrin as drying agent, while the control yielded 9.5 ± 1.8%. Furthermore, it was found that the spray-dried product could recover more than 90% of the TPC and betacyanin in the extracts, which indicates that spray drying may be suitable for heat-sensitive materials.

Impact of the Purification Process on the Spray-Drying Performances of the Three Families of Lipopeptide Biosurfactant Produced by Bacillus subtilis

Lipopeptides produced by Bacillus subtilis display many activities (surfactant, antimicrobial, and antitumoral), which make them interesting compounds with a wide range of applications. During the past years, several processes have been developed to enable their production and purification with suitable yield and purity. The already implemented processes mainly end with a critical drying step, which is currently achieved by freeze-drying. In this study, the possibility to replace this freeze-drying step with a spray-drying one, more suited to industrial applications, was analyzed. After evaluating their thermal resistance, we have developed a spray-drying methodology applicable for the three lipopeptides families produced by B. subtilis, i.e., surfactin, mycosubtilin (iturin family), and plipastatin (fengycin family). For each lipopeptide, the spray-drying procedure was applied at three steps of the purification process by ultrafiltration (supernatant, diafiltered solution, and pre-purified fraction). The analysis of the activities of each spray-dried lipopeptide showed that this drying method is not decreasing its antimicrobial and biosurfactant properties. The methodology developed in this study enabled for the first time the spray-drying of surfactin, without adjuvants’ addition and regardless of the purification step considered. In the case of fengycin and mycosubtilin, only diafiltered solution and purified fraction could be successfully spray-dried without the addition of adjuvant. Maltodextrin addition was also investigated as the solution for the direct drying of supernatant. As expected, the performances of the spray-drying step and the purity of the powder obtained are highly related to the purification step at which the product was dried. Interestingly, the impact of mycosubtilin concentration on spray-drying yield was also evidenced.