Smart phase transformation system based on lyotropic liquid crystalline@hard capsules for sustained release of hydrophilic and hydrophobic drugs

Smart phase transformation systems@hard capsule (SPTS@hard capsule) based on lyotropic liquid crystalline (LLC) were developed for oral sustained release in this study. Doxycycline hydrochloride (DOXY) and meloxicam (MLX) were used as hydrophilic and hydrophobic model drug, respectively. Two systems were added with different additives, that is, gelucire 39/01, PEG 1000 and Tween 80 to adjust their melting point and release profiles. The phase transformation of these systems could be triggered by water as well as temperature. They could spontaneously transform into cubic phase or hexagonal phase when coming across with water, to achieve the 24 h sustained release profile. In addition, the obtained systems could switch between semisolid state and liquid state when temperature changed within room temperature and body temperature, which facilitated the phase transformation in gastrointestinal tract and during their encapsulation into hard capsules. LLC-based SPTS@hard capsule revealed potential for the industrialization of its oral administration on account of its drugs accommodation with different solubility, controllable release profile and simple preparation process

Moisture-Resistant Co-Spray-Dried Netilmicin with <span style="font-variant: small-caps">l</span>-Leucine as Dry Powder Inhalation for the Treatment of Respiratory Infections

Netilmicin (NTM) is one of the first-line drugs for lower respiratory tract infections (LRTI) therapy, but its nephrotoxicity and ototoxicity caused by intravenous injection restrict its clinical application. Dry powder inhalation (DPI) is a popular local drug delivery system that is introduced as a solution. Due to the nature of NTM hygroscopicity that hinders its direct use through DPI, in this study, L-leucine (LL) was added into NTM dry powder to reduce its moisture absorption rate and improve its aerosolization performance. NTM DPIs were prepared using spray-drying with different LL proportions. The particle size, density, morphology, crystallinity, water content, hygroscopicity, antibacterial activity, in vitro aerosolization performance, and stability of each formulation were characterized. NTM DPIs were suitable for inhalation and amorphous with a corrugated surface. The analysis indicated that the water content and hygroscopicity were decreased with the addition of LL, whilst the antibacterial activity of NTM was maintained. The optimal formulation ND2 (NTM:LL = 30:1) showed high fine particle fraction values (85.14 &#177; 8.97%), which was 2.78-fold those of ND0 (100% NTM). It was stable after storage at 40 &#177; 2 &#176;C, 75 &#177; 5% relative humidity (RH). The additional LL in NTM DPI successfully reduced the hygroscopicity and improved the aerosolization performance. NTM DPIs were proved to be a feasible and desirable approach for the treatment of LRTI

Low density, good flowability cyclodextrin-raffinose binary carrier for dry powder inhaler: anti-hygroscopicity and aerosolization performance enhancement

<p><b>Background</b>: The hygroscopicity of raffinose carrier for dry powder inhaler (DPI) was the main obstacle for its further application. Hygroscopicity-induced agglomeration would cause deterioration of aerosolization performance of raffinose, undermining the delivery efficiency.</p> <p><b>Methods</b>: Cyclodextrin-raffinose binary carriers (CRBCs) were produced by spray-drying so as to surmount the above issue. Physicochemical attributes and formation mechanism of CRBCs were explored in detail. The flow property of CRBCs was examined by FT4 Powder Rheometer. Hygroscopicity of CRBCs was elucidated by dynamic vapor sorption study. Aerosolization performance was evaluated by <i>in vitro</i> deposition profile and <i>in vivo</i> pharmacokinetic profile of CRBC based DPI formulations.</p> <p><b>Results</b>: The optimal formulation of CRBC (R₄) was proven to possess anti-hygroscopicity and aerosolization performance enhancement properties. Concisely, the moisture uptake of R₄ was c.a. 5% which was far lower than spray-dried raffinose (R₀, c.a. 65%). R₄ exhibited a high fine particle fraction value of 70.56 ± 0.61% and it was 3.75-fold against R₀. The pulmonary and plasmatic bioavailability of R₄ were significantly higher than R₀ (<i>p</i> < 0.05).</p> <p><b>Conclusion</b>: CRBC with anti-hygroscopicity and aerosolization performance enhancement properties was a promising approach for pulmonary drug delivery, which could provide new possibilities to the application of hygroscopic carriers for DPI.</p