NIOSOMES AS AN APPROACH TO IMPROVE THE SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS II DRUGS Review Article GAURANG SAWANT 1* , GEETA BHAGWAT 1 1 Department of Pharmaceutics, H. K. College of Pharmacy, Oshiwara, Mumbai, India * Received: 01 Dec 2020, Revised and Accepted: 30 Jan 2021 Email: sawant.gaurang10@gmail.com ABSTRACT Based on their solubility and permeability, drugs are typically divided into four classes (Classes I–IV) according to the biopharmaceutics classification system (BCS). Of these classes, BCS class II drugs have high permeability and low solubility; not only do these characteristics constitute the rate-limiting step in the formulation of these drugs but the low solubility in water results in low bioavailability. Thus, methods for improving their solubility have been developed using lipid carriers such as liposomes, niosomes, and aquasomes; other approaches include self-micro- emulsifying drug delivery systems (SMEDDS) and self-nano-emulsifying drug delivery systems (SNEDDS). Currently, niosome-based drug delivery systems that utilize nonionic surfactants, drugs, and cholesterol in varying ratios are being widely used to deliver both hydrophilic and lipophilic drugs in addition to several other applications of niosomes. Keywords: Biopharmaceutics, Solubility, Permeability, Lipid carriers, Liposomes, Niosomes © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2021v13i2.40423. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION The biopharmaceutics classification system (BCS) is a useful mechanism used by researchers for obtaining biowaivers during in vivo bioequivalence studies and for decision making when determining the required solubility and permeability during drug discovery. This is because BCS is established upon a scientific blueprint highlighting the three rate-limiting steps critical in oral absorption: the liberation of the drug from its dosage form [1], prolongation of the dissolved state along with the whole gastrointestinal (GI) tract [2], and penetration of the drug molecules via the GI membrane into the blood [3]. Additionally, enterohepatic metabolism constitutes a fourth step that affects the systemic accessibility along with the release of metabolites into systemic blood circulation. The biopharmaceutical drug disposition classification system (BDDCS) proposed by Wu and Benet comprehensively describes the absorption operation by including the fourth rate-limiting step of first-pass metabolism. Niosomes are uncharged surfactant vesicles comprising microscopic lamellar structures built upon an amalgamation of uncharged surfactants such as the alkyl or dialkyl polyglycerol ether class and cholesterol formed via subsequent hydration in an aqueous buffer [2]. In niosomes, the vesicle-building amphiphiles are uncharged surfactants (e. g., Span 60) that are typically balanced by incorporating cholesterol and minuscule amounts [1.5 mg] of a negatively charged surfactant such as dicetyl phosphate [4]. Several methods exist for niosome fabrication such as ether injection [5, 6], the hand-shaking method [6], sonication [6], microfluidization [7], reverse phase evaporation [8], the bubble method [9], multiple membrane extrusion [7], and the proniosomal approach [10]. Characterization parameters include particle size, in vitro drug release, entrapment efficiency, and drug content together with some specific characteristics that depend on the formulation mechanism such as skin permeation etc. Herein, a literature survey was performed using accessible databases such as Google Scholar, PubMed, and Scopus to review research articles and thus compile a comprehensive yet concise introduction to the BCS and niosomes along with their applications. Biopharmaceutics classification system BCS is a scientific framework for classifying a drug based on its aqueous solubility and intestinal penetrability [11]. When used in conjunction with the in vitro dissolution properties of the concerned drug, BCS considers three important parameters: solubility, intestinal permeability, and dissolution rate. Together these parameters determine the essential factors of the speed and limit of oral drug absorption from immediate- release (IR) solid oral dosage forms [12, 13]. Based on the BCS framework, the drugs can be classified into four basic groups using the criteria of their solubility and permeability toward gastrointestinal tract (GIT) mucosa, as shown in fig. 1. The solubility categorization of a drug in the BCS is determined on the basis of the maximum dosage strength of the IR product. A drug is deemed highly soluble when its maximum dosage strength is soluble in a minimum of 250 ml of water-based media spanning a pH range of 1.0–7.5; otherwise, the drug is deemed a poorly soluble candidate. The volume approximation of 250 ml was established in the literature using traditional bioequivalence study methods [12, 13]. The permeability classification is directly based on a drug’s intestinal absorption limit in humans or indirectly based on the calculations of mass transfer speed via the human intestinal membrane. A drug is deemed highly permeable when the intestinal absorption limit is ≥90%. Otherwise, the drug is deemed poorly permeable [12, 13]. An IR drug is categorized as a fast dissolution product when at least 85% of the stated amount of the drug dissolves in less than 30 min when utilizing the United States Pharmacopoeia (USP) Apparatus I set at 100 rotations per minute (rpm) or USP Apparatus II at 50 rpm comprising a minimum volume of 900 ml of each of the following media: 1) acidic media, such as 0.1 N hydrochloric acid or USP simulated gastric fluid with an absence of enzymes; 2) a pH 4.5 buffer, and 3) a pH 6.8 buffer or USP simulated intestinal fluid in the absence of enzymes. Otherwise, the drug is deemed a slow dissolution product. Fig. 1: Biopharmaceutics classification system †‡† Adapted from commons. wikimedia.org, by MKD 2020 https://commons.wikimedia.org/wiki/File:Biopharmaceutics_ Classification_System_(BCS).jpg. Copyright by, MKD 2020, ‡ Copyright permission obtained under license CC BY 4.0 (Creative Commons Attribution-Share Alike 4.0 International ) International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 13, Issue 2, 2021