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    Paclitaxel-loaded micro or nano transfersome formulation into novel tablets for pulmonary drug delivery via nebulization

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    Khan and Elhissi 2020 - IJP.pdf (2.007Mb)
    Date
    2020-02-15
    Author
    Iftikhar, Khan
    Apostolou, Maria
    Bnyan, Ruba
    Houacine, Chahinez
    Elhissi, Abdelbary
    Yousaf, Sakib S
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    Abstract
    A simplistic approach was adopted to manufacture novel paclitaxel (PTX) loaded protransfersome tablet formulations for pulmonary drug delivery. The large surface area offered by the pulmonary system acts as a desirable site for anti-cancer drug deposition; offering localized effect within the lungs. Protransfersomes are dry powder formulations, whereas transfersomes are liquid dispersions containing vesicles generated from protransfersomes upon hydration. Protransfersome powder formulations (F1–F27) (referred as Micro formulations based on transfersomes vesicles size post hydration) were prepared by employing a phospholipid (Soya phosphatidylcholine (SPC)), three different carbohydrate carriers (Lactose monohydrate, LMH; Microcrystalline cellulose, MCC; and Starch), three surfactants (i.e. Span 80, Span 20 and Tween 80) in three different lipid phase to carrier ratios (i.e. 1:05, 1:15 and 1:25 w/w), with the incorporation of PTX as a model drug. Hydrophobic chain of SPC may enhance PTX solubility, entrapment and targetted delivery via transfersome vesicles. Out of the 27 Micro protransfersome formulations, PTX-loaded LMH powder formulations F3, F6 and F9 (i.e. 1:25 w/w lipid phase to carrier ratio) exhibited excellent powder flowability via angle of repose (AOR) and good compressibility index due to associated smaller and uniform particle size and shape of LMH. Following hydration, these formulations also showed smaller volume median diameters (VMD) in micrometres (5.65 ± 0.85–6.76 ± 0.61 µm) and PTX entrapment of 93–96%. Hydrated transfersome formulations (F3, F6 and F9) were converted into Nano size via probe sonication and referred to as Nano formulations. These Nano formulations were converted into dry powder via spray drying (SD) (F3NSD, F6NSD and F9NSD) or freeze drying (FD) (F3NFD, F6NFD and F9NFD). Post manufacture of protransfersome tablets (i.e. 9 formulations), quality control tests were conducted in accordance to British Pharmacopeia (BP). Only the Micro formulations protransfersome tablets (i.e. F3, F6 and F9) passed the uniformity of weight test, exhibited high crushing strength and tablet thickness when compared to SD or FD protransfersome tablets. Micro protransfersome formulations (i.e. F3, F6 and F9) into tablets demonstrated a shorter nebulization time and high output rate when using Ultrasonic nebulizer compared to Vibrating mesh nebulizer (i.e. Omron NE U22). Based on formulations, characterizations and nebulizer performance; Micro protransfersome tablet formulations F3, F6 and F9 (i.e. 1:25 w/w) and Ultrasonic nebulizer were found to be a superior combination, eliciting enhanced output efficiency. Moreover, PTX-loaded F3, F6 and F9 tablet formulations (10%) exhibited toxicity (60, 68 and 67% cell viability) to cancer MRC-5 SV2 (i.e. immortalized human lung cells) while safe to MRC-5 (normal lung fibroblast cells) cell lines.
    URI
    https://www.sciencedirect.com/science/article/pii/S0378517319309640
    DOI/handle
    http://dx.doi.org/10.1016/j.ijpharm.2019.118919
    http://hdl.handle.net/10576/17270
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