Original Article SPRAY DRIED LACTOSE BASED PRONIOSOMES AS STABLE PROVESICULAR DRUG DELIVERY CARRIERS: SCREENING, FORMULATION, AND PHYSICOCHEMICAL CHARACTERIZATION ALI NASR 1,2* , MONA QUSHAWY 1,3 , SHADY SWIDAN 4 1 Department of Pharmaceutics, Faculty of Pharmacy, Sinai University, Alarish, Egypt, 2 Department of Pharmaceutics, Faculty of Pharmacy, Port Said University, Port Said, Egypt, 3 Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia, 4 Received: 05 Jun 2018, Revised and Accepted: 16 Jul 2018 ABSTRACT Objective: In the present investigation efforts were considered to optimize the different conditions for the preparation of spray dried lactose based proniosomes. The aim of this research was to investigate the feasibility of proniosomes as stable precursors for the development of niosomes as oral drug delivery system for poorly water-soluble drugs. Methods: A total of twenty-eight plain proniosomal formulae were prepared with various surfactant-cholesterol loading ratios in each formula using spray dried lactose as a carrier. Span 20, 40, 60 and 80 were used in various molar ratios with cholesterol. Different evaluation techniques were performed to study the performance of the prepared proniosomes. The micromeritic properties of the prepared proniosomes were analyzed. The reconstituted niosomes were further evaluated for morphological characterization using transmission electron microscope (TEM), particle size analysis, zeta potential, and polydispersity index (PDI). Finally, selected proniosomal formulae were tested for stability study. Results: The proniosomal formulae prepared using span 40 and span 60 exhibited excellent flowability while those prepared with span 20 and span 80 showed poor flow properties. TEM photographs revealed that the vesicles were discrete, spherical without aggregation. The mean vesicle size of reconstituted niosomes was found to be in the range between (252.9±0.43–624.3±0.23 nm) with perfect PDI values (0.387±0.05–0.835±0.03). The negative values of zeta potential indicated that all prepared formulae were stabilized by electrostatic repulsion forces. Stability studies confirmed that proniosomes give a more stable system that could overcome the problems of standard niosomes. Formulae with the smallest particle size, higher surface charge values and best flow properties were selected to be loaded with poorly soluble drugs for further study. Conclusion: The obtained results offered evidence that spray-dried lactose based proniosomes are promising stable drug delivery carriers and ready to incorporate various poorly water-soluble drugs in order to improve their limited oral bioavailability. Department of Pharmaceutics, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt Email: ali.nasr@su.edu.eg Keywords: Proniosomes, Spray dried lactose, Surfactant, Cholesterol, Drug delivery carrier and Bioavailability © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2018v10i5.27732 INTRODUCTION Over the decades, the oral route remains the most preferred route of administration for drug delivery. However, a plurality of the new and present drugs taken by oral route usually face bioavailability drawbacks [1]. Different approaches have been employed for improving the dissolution profile of poorly water-soluble drugs [2]. Considerable interest has been focused on the design and formulation of new drug delivery systems. Among them, vesicular drug delivery systems are of high significance. There are different types of vesicular drug delivery systems such as liposomes, niosomes, transferosomes, ethosomes, colloidosomes, and cubosomes. Novel approaches like provesicular drug delivery systems such as proniosomes, layerosomes and ufosomes have also been developed which have higher stabilities compared to conventional and simple vesicular systems [3]. Provesicular systems can be used for prolonged and targeted drug delivery with mild side effects and also provides patient compliance by decreasing the administered dose. Colloidal particulate drug delivery systems such as liposomes [4] or niosomes [5] are very distinguished in comparison to conventional dosage forms because these vesicular systems can act as drug- containing reservoirs and alter the particle composition or surface to adjust the drug release or the affinity of the drug for the target site. Niosomes are nonionic surfactant vesicles which can entrap both hydrophilic and hydrophobic drugs [6]. Niosomes proved to be an alternative to liposomes because they have more chemical stability and economical as compared to liposomes. But though niosomes reveal good chemical stability, there may be drawbacks of physical instability concerning the dispersions. Similar to liposomes, aqueous niosomal dispersions may show aggregation, fusion, leakage of included drugs, or hydrolysis of encapsulated drugs, thus reducing the shelf life of niosomes [7]. So as to overcome the stability troubles concerning niosomes, proniosomes (dry niosomes) were developed. Proniosomes are dried powder, free flowable, granular product which upon dilution with water develops niosomal dispersion convenient for oral administration [8]. The niosomes formed after reconstitution is analogous to conventional niosomes, however, have uniform size [9]. Different nonionic surfactants with varying HLB were used in the preparation of proniosomes such as polyoxyethylene sorbitan esters (Tweens) [10], polyoxyethylene alkyl ethers (Brijs) and sorbitan esters (spans) [11]. It was noticed that for optimum proniosomes formulations which achieved smaller particle size, and higher entrapment efficiency is obtained within the HLB range from 1 to 8, which is the range of spans [12]. Cholesterol provides rigidity to the niosomes after the hydration of proniosomes and decreases drug leakage, thus increasing the entrapment efficiency. It also stabilizes the structure of the niosomes by inhibition of aggregate formation by exerting steric effect [13]. Different carriers are used in the formation of the dry proniosomes such as: mannitol, sorbitol, lactose and maltodextrin. The desired properties of the carrier include; non-toxicity and in vivo safety, poor solubility in the solvent of the loaded solution, free flowability, and excellent water solubility for easy and instant hydration [14]. Spray dried lactose shows optimum behavior as a carrier in proniosomal systems as it has a spherical shape and best flowability among other carriers [15]. There are the various method used for the preparation of proniosomes which include a slurry method and the spraying of International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 10, Issue 5, 2018