A Facile and Novel Approach to Manufacture Paclitaxel-Loaded Proliposome Tablet Formulations of Micro or Nano Vesicles for Nebulization

Abstract

Purpose The aim of this study was to develop novel paclitaxel-loaded proliposome tablet formulations for pulmonary drug delivery. Method Proliposome powder formulations (i.e. F1 – F27) were prepared employing Lactose monohydrate (LMH), Microcrystalline cellulose (MCC) or Starch as a carbohydrate carriers and Soya phosphatidylcholine (SPC), Hydrogenated soya phosphatidylcholine (HSPC) or Dimyristoly phosphatidylcholine (DMPC) as a phospholipid. Proliposome powder formulations were prepared in 1:5, 1:15 or 1:25 w/w lipid phase to carrier ratio (lipid phase; comprising of phospholipid and cholesterol in 1:1 M ratio) and Paclitaxel (PTX) was used as model anticancer drug. Results Based on flowability studies, out of 27 formulations; F3, F6, and F9 formulations were selected as they exhibited an excellent angle of repose (AOR) (17.24 ± 0.43, 16.41 ± 0.52 and 15.16 ± 0.72°), comparatively lower size of vesicles (i.e. 5.35 ± 0.76, 6.27 ± 0.59 and 5.43 ± 0.68 μm) and good compressibility index (14.81 ± 0.36, 15.01 ± 0.35 and 14.56 ± 0.14) via Carr’s index. The selected formulations were reduced into Nano (N) vesicles via probe sonication, followed by spray drying (SD) to get a dry powder of these formulations as F3SDN, F6SDN and F9SDN, and gave high yield (>53%) and exhibited poor to very poor compressibility index values via Carr’s Index. Post tablet manufacturing, F3 tablets formulation showed uniform weight uniformity (129.40 ± 3.85 mg), good crushing strength (14.08 ± 1.95 N), precise tablet thickness (2.33 ± 0.51 mm) and a short disintegration time of 14.35 ± 0.56 min, passing all quality control tests in accordance with British Pharmacopeia (BP). Upon nebulization of F3 tablets formulation, Ultrasonic nebulizer showed better nebulization time (8.75 ± 0.86 min) and high output rate (421.06 ± 7.19 mg/min) when compared to Vibrating mesh nebulizer. PTX-loaded F3 tablet formulations were identified as toxic (60% cell viability) to cancer MRC-5 SV2 cell lines while safe to normal MRC-5 cell lines. Conclusion Overall, in this study LMH was identified as a superior carbohydrate carrier for proliposome tablet manufacturing in a 1:25 w/w lipid to carrier ratio for in-vitro nebulization via Ultrasonic nebulizer.

Recent Advances in the Microencapsulation of Essential Oils, Lipids, and Compound Lipids through Spray Drying: A Review

“…In food applications, they are used due to their antimicrobial, insecticidal, and antifungal characteristics. On the other hand, in the pharmaceutical industry, health benefits are sought in various diseases such as cancer [ 157 , 158 , 159 ], stress, antisicosis [ 160 ], obesity [ 161 , 162 ], diabetes, antidiabetic, hypolipidemic, anti-inflammatory [ 163 ], tuberculosis [ 164 ], the polyneuropathy of hereditary transthyretin [ 165 ], and acne [ 166 ].…”

Development of Paclitaxel Proliposomal Dry Powder Inhaler (PTX-PLM-DPI) by Freeze-Drying Method for Lung Cancer

“…The bulk and tapped densities, Carr's index, Hausner's ratio and angle of reposewere determined to measure the flow property of the PLM-based DPI powders, pre-and postlyophilized [37]. The bulk density and tapped density of the PLM powder sample were calculated using a graduated measuring cylinder (100 mL) in a mechanical tapped density apparatus (ROLEX).…”

Transferosomes as a transdermal drug delivery system: Dermal kinetics and recent developments

“…Transferosomes are supple or malleable vesicles invented in the early 1990s. The term “transferosome” is a combination of Latin and Greek, derived from the meaning “to carry the body” (Khan et al, 2020). Currently, the use of transferosomes‐based TDD has attracted a lot of attention in the pharmaceutical research circles (Akram et al, 2021).…”