International Journal of Pharmaceutics 428 (2012) 96–102 Contents lists available at SciVerse ScienceDirect International Journal of Pharmaceutics journa l h omepa g e: www.elsevier.com/locate/ijpharm A flow system for the on-line quantitative measurement of the retention of dosage forms on biological surfaces using spectroscopy and image analysis Richard A. Cave, Joseph P. Cook, Che J. Connon, Vitaliy V. Khutoryanskiy ∗ Reading School of Pharmacy, University of Reading, Reading, Berkshire RG6 6AD, UK a r t i c l e i n f o Article history: Received 30 October 2011 Received in revised form 27 February 2012 Accepted 28 February 2012 Available online 7 March 2012 Keywords: Bioadhesion Mucoadhesion Image analysis UV/vis spectroscopy In vitro models Residence time Drug delivery a b s t r a c t Measuring the retention, or residence time, of dosage forms to biological tissue is commonly a qualitative measurement, where no real values to describe the retention can be recorded. The result of this is an assessment that is dependent upon a user’s interpretation of visual observation. This research paper outlines the development of a methodology to quantitatively measure, both by image analysis and by spectrophotometric techniques, the retention of material to biological tissues, using the retention of polymer solutions to ocular tissue as an example. Both methods have been shown to be repeatable, with the spectrophotometric measurement generating data reliably and quickly for further analysis. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Bioadhesion is defined as the attachment of synthetic or natural materials to biological surfaces. In pharmaceutics this phenomenon has often been exploited by using the ability of different polymers to adhere to mucosal surfaces and provide prolonged retention of dosage forms, resulting in improved drug bioavailability (Peppas and Sahlin, 1996; Smart, 2005; Bernkop-Schnurch, 2005; Serra et al., 2009; Andrews et al., 2009; Khutoryanskiy, 2011). The excel- lent potential of mucoadhesive dosage forms has been recognized in buccal, nasal, ocular and vaginal drug delivery and a number of novel pharmaceutical technologies utilizing mucoadhesion have been commercialized. Recent reports have suggested that the mar- ket for mucoadhesive drug delivery systems is expanding rapidly (Andrews et al., 2009). Mucoadhesive dosage forms can be formulated as tablets, films, powders, pellets, solutions and gels. A number of methods have been developed for evaluating the mucoadhesive properties of var- ious formulations. The most common in vitro methods include tensile studies, visual detachment/dissolution time determination, rheological and flow retention techniques (Peppas and Sahlin, 1996; Khutoryanskiy, 2011). The flow retention technique first described by Rango Rao and Buri (1989) is often used for estimating the mucoadhesive ∗ Corresponding author. Tel.: +44 0118 378 6119; fax: +44 0118 378 4703. E-mail address: v.khutoryanskiy@reading.ac.uk (V.V. Khutoryanskiy). properties of dosage forms administered in regions of the human body where formulations are affected by the flow of biological flu- ids. For example, it can be used for testing gastrointestinal, ocular, nasal or vaginal formulations and it involves simulation of a bio- logical flow which washes off a dosage form from the surface of a mucosal tissue. This technique can typically be used for evaluating mucoadhesive properties of micro-particles and nano-particles as well as liquid and semi-solid formulations (e.g., syrups, gels and creams). Different variants of this technique have been successfully used and described in pharmaceutical literature. In the original pub- lication, Rango Rao and Buri (1989) used this technique with 0.45–0.50 mm glass beads coated with various mucoadhesive poly- mers. They estimated the retention potential of different polymers by measuring the mass of beads washed off a mucosal surface by simulated gastric juice or phosphate buffer solution. Mikos and Peppas (1990) proposed the use of a video camera to monitor the retention of a single polymer microparticle on mucosal tissue in a flow channel and discussed the theoretical basis of flow phe- nomena in this system. Nielsen et al. (1998) have applied the flow method to evaluate the adhesion of glyceryl monooleate (GMO) and glyceryl monolinoleate (GML) cubic phase gel formulations to rabbit stomach, buccal and intestinal mucosal tissues. They used high performance liquid chromatography (HPLC) to deter- mine the concentration of GMO/GML in the effluent collected after 30 min, and used this to estimate the amount of gel remaining on the surface of the mucosal tissue. Belgamwar and Surana (2010) used a similar technique for evaluating the retention potential of 0378-5173/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2012.02.047