RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology Lipid-Based Formulations Solidified Via Adsorption onto the Mesoporous Carrier Neusilin R  US2: Effect of Drug Type and Formulation Composition on In Vitro Pharmaceutical Performance HYWEL D. WILLIAMS, 1 MICHIEL VAN SPEYBROECK, 2 PATRICK AUGUSTIJNS, 2 CHRISTOPHER J. H. PORTER 1 1 Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia 2 Drug Delivery and Disposition, KU Leuven, Leuven, Belgium Received 10 February 2013; revised 18 March 2014; accepted 25 March 2013 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.23970 ABSTRACT: The current study determined the extent to which the desorption of lipid-based formulations (LBFs) from a mesoporous magnesium aluminometasilicate (Neusilin R  -US2) carrier is governed by drug properties, LBF composition, and LBF-to-adsorbent ratio. A secondary objective was to evaluate the impact of testing parameters (medium composition, pH, dilution, and agitation) on in vitro LBF performance. Two self-emulsifying LBFs, with high/low lipid–surfactant ratios were studied in detail using danazol, fenofibrate, cinnarizine, and mefenamic acid as model drugs. A wider range of 38 different danazol-containing LBF were also evaluated, where desorption was evaluated immediately after preparation and after 1 month of storage. The results revealed that incomplete desorption from Neusilin R  was a feature of all drugs and LBFs tested. Desorption was insensitive to agitation but increased under conditions where ionizable drugs were charged. In addition, formulations containing a higher proportion (>30%) of hydrophilic surfactant consistently exhibited higher desorption, and were least susceptible to decreased desorption on storage. In summary, although Neusilin R  is an effective vehicle for LBF solidification, its use is accompanied by a risk of incomplete desorption of the vehicle from the carrier, irrespective of the drug. Lipid Formulation Classification System (LFCS)Type IIIB LBFs comprising higher quantities of hydrophilic surfactants appear to desorb most from Neusilin R  . C  2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci Keywords: poorly water-soluble drugs; lipids; self-emulsifying; adsorption; lipid-based formulations; self-emulsifying drug delivery sys- tems; neusilin R  ; adsorbents INTRODUCTION Concurrent with the realization that an increasing number of drugs under development have low-aqueous solubility, efforts to develop new formulation strategies and to better understand the existing formulation strategies are also increasing. 1 Lipid- based formulations (LBFs) represent one such formulation strategy. 2,3 Improvements in drug bioavailability after admin- istration of poorly water-soluble drugs in LBFs are commonly attributed to avoidance of traditional dissolution processes, 4,5 an ability to stimulate lipid digestion and to enrich the gas- trointestinal tract with endogenous solubilizers (bile salts and phospholipids), 6,7 the potential to recruit intestinal lymphatic transport processes and to bypass first-pass metabolism, 8 and, finally, the opportunity to promote supersaturation and to in- crease thermodynamic activity at the absorptive site. 9,10 In recent years, there has been increasing interest in strate- gies that enable the solidification of liquid and semi-solid LBF 11,12 to enable the production of free-flowing powders that may be transformed into solid compacts and/or powder-filled capsules. 13 A powder-filled capsule may be particularly attrac- Correspondence to: Christopher J. H. Porter (Telephone: +61-3-9903-9649; Fax: +61-3-9903-9583; E-mail: chris.porter@monash.edu) Hywel D. Williams’ present address is Capsugel Product Development Centre, 200 Technology Square, Cambridge, Massachusetts 02139. Michiel Van Speybroeck’s present address is Formac Pharmaceuticals, Gaston Geenslaan 1, Heverlee 3001, Belgium. This article contains supplementary material available from the authors upon request or via the Internet at http://onlinelibrary.wiley.com/. Journal of Pharmaceutical Sciences C  2014 Wiley Periodicals, Inc. and the American Pharmacists Association tive for convenience purposes because additional excipients may not be required. However, low powder density may limit capsule loading to only a few hundred milligrams. On the con- trary, a tableting approach offers the potential to convert a sig- nificant mass of liquid-loaded powder (as much as a gram) into a single compact, 16 but in this case, significant formulation ef- forts may be required to produce robust tablets that show rapid rates of disintegration. One popular technique for LBF solidification is the adsorp- tion of the LBF directly onto high-surface-area adsorbents such as Aerosil R  , Hubersorb R  , Sylysia R  , and Neusilin R  . 13–15 Neusilin R  US2, a magnesium alumino metasilicate in granular form, has been most widely investigated for this application, as it has a high absorbent capacity for liquid substances, 13,15–17 and good flowability 13 and tabletability. 17 However, despite the attractiveness of this approach, we have previously shown using two exemplar self-emulsifying drug delivery systems (SEDDS) that in vitro and in vivo performance can be re- duced when compared with the equivalent liquid SEDDS. 15 A mechanism for this performance differential was postulated, and suggested to reflect incomplete desorption of liquid formu- lation components, and therefore, incomplete release of drug from the carrier. The subsequent lower concentrations of sol- ubilized drug (typically decreased to ∼65% of maximum) ulti- mately led to decreased drug absorption in vivo. 15 These stud- ies were consistent with those of others 13,18 underscoring the seemingly broad applicability of this phenomenon to different drugs, formulations, and carriers. In contrast, however, other studies have reported complete formulation desorption from similar systems. 16,19–21 The presence of contradictory reports Williams et al., JOURNAL OF PHARMACEUTICAL SCIENCES 1