Chapter 9 - Nanoliposomal dry powder formulations

Abstract

Liposomal dry powder formulations (DPFs) have proven their superiority over conventional DPFs due to favorably improved pharmacokinetics and pharmacodynamics of entrapped drugs, and thus, reduced local and systemic toxicities. Nanoliposomal DPFs (NLDPFs) provide stable, high aerosolization efficiency to deep lung, prolonged drug release, slow systemic dilution, and avoid macrophage uptake of encapsulated drug by carrier-based delivery of nano-range liposomes. This chapter describes methods of preparation of nanoliposomes (NLs) and NLDPFs, using various techniques, and their characterization with respect to size distribution, flow behavior, in vitro drug release profile, lung deposition, cellular uptake and cytotoxicity, and in vivo pharmacokinetics and pharmacodynamics. Some examples have been detailed for better understanding of the methods of preparation and evaluation of NLDPFs by investigators.

Figure 9.1

(A) Detailed flow chart describing formulation optimization of nanoliposomes and (B) detailed flow chart describing formulation optimization of NLDPFs.

Figure 9.2

Particle size distribution of amiloride hydrochloride NLDPFs. (Reprinted with permission from Chougule et al.(2006). Copyright © American Scientific Publishers, www.aspbs.com.)

Figure 9.3

Scanning electron micrograph (A) and surface texture analysis (B) of dapsone NLDPF. (With kind permission from Springer Science + Business Media: Chougule et al. (2008).

Figure 9.4

Differential scanning calorimetric graphs of developed amiloride hydrochloride NLDPF (a), plain drug (b), and physical mixture (c). (Reprinted with permission from Chougule et al. (2006). Copyright © American Scientific Publishers, www.aspbs.com.)

Figure 9.5

In vitro release profile of developed amiloride hydrochloride NLDPFs and plan drug DPFs (SAHL = plain drug formulation, SLDPIM = NLDPF containing mannitol, SLDPIL = NLDPF containing lactose, and SLDPFs = NLDPF containing sucrose). (Reprinted with permission from Chougule et al. (2006). Copyright © American Scientific Publishers, www.aspbs.com.)

Figure 9.6

Intratracheal instillations and bronchoalveolar lavage on rat.

Figure 9.7

Astra-type liquid cascade impinger used with a Transwell under the second-stage nozzle. (With kind permission from Springer Science + Business Media: Fiegel et al. (2003)).

Figure 9.8

Isolated perfused rat lung (IPRL) preparations of (A) Horizontally positioned IPRL with a scheme of forced solution instillation and (B) vertically positioned IPRL with a scheme of nebulization catheter dosing. (Reprinted from Sakagami et al. (2006). Copyright 2006, with permission from Elsevier.)