A recent AAPS Open article investigates polymer membrane surface modifications for production of biomimetic membranes.
By Michael M. Puppolo, head of Analytical Development, Hovione, N.J.
With the cost of drug development exceeding $2.5 billion dollars1,2 for a single new pharmaceutical drug product, the importance of enhancing efficiency in pharmaceutical R&D is evident. Researchers are now implementing innovative ideas that provide links between manufacturing / product design and clinical safety / efficacy,3 thereby reducing development costs. Focusing on preclinical drug development, in vitro dissolution testing has proven to be an indispensable tool that can be used to predict in vivo dissolution performance and bioavailability. Biorelevant in vitro dissolution techniques often entail mimicking mass transport of drug molecules across the mucosa layer and epithelial membrane,4 thus providing a mechanistic understanding of drug speciation and free drug absorption.5 The AAPS Open article Plasma modification of microporous polymer membranes for application in biomimetic dissolution studies6 evaluates one such investigation involving polymer membrane surface modifications for production of biomimetic membranes to be employed in biorelevant in vitro dissolution studies.
Industry-accepted in vitro dissolution methodologies expend numerous resources to emulate in vivo dissolution conditions. Existing membrane-permeation in vitro dissolution techniques use membranes that are expensive to manufacture and may be unrepresentative of the intestinal epithelium as they exhibit thick unstirred aqueous layers, large molecular weight cut-offs, and limited stability in buffered environments. In our AAPS Open article, plasma modification of polymer membranes was presented as a viable solution to existing artificial and cell-based membrane limitations. We note that the success of plasma-modified microporous membranes can potentially be associated with advantageous factors such as cost, lifetime, chemical/pH compatibility, and control over the depth of the unstirred aqueous layer.
To be defined as “biomimetic,” the plasma-treated microporous polymer membranes should exhibit physiologically relevant properties associated with the intestinal epithelial membrane. Membranes portraying hydrophilic and hydrophobic properties that simulate the lipophilic constituents and unstirred aqueous layer of the intestinal membrane would epitomize the meaning of biomimetic with reference to in vitro dissolution testing. Our article presents the application of low temperature plasma treatment of microporous polyethersulfone, nylon, and polypropylene polymer membranes to produce low energy surface layers with permanent hydrophobic and hydrophilic functionalities. Surface modifications on microporous polymer membranes were achieved by plasma treatments using tetrafluoromethane, perfluorohexane, dichloromethane, and water. Surface characterization of treated membranes was evaluated using scanning electron microscopy energy dispersive X-ray spectroscopy, water contact angle, and X-ray photoelectron spectroscopy techniques.
Plasma modification of microporous polymer membranes for application in biomimetic dissolution studies encompasses numerous scientific topics that relate to research in a variety of fields including surface modification, early stage drug and formulation development, dissolution testing, and surface characterization. In supplemental studies, the authors present detailed comparisons of the plasma-treated microporous polymer membranes with porcine intestines5 as well as in vitro-in vivo comparisons of the plasma-treated microporous polymer membranes with in vivo mice studies,7 thereby revealing the true biomimetic nature of the plasma-modified membranes.
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- Mullin R. Cost to Develop New Pharmaceutical Drug Now Exceeds $2.5B. Scientific American. November 24, 2014. Accessed March 7, 2018.
- Dickinson PA, Lee WW, Stott PW, et al. Clinical Relevance of Dissolution Testing in Quality by Design. AAPS J. 2008;10(2):380–390.
- Amidon GL, Sinko PJ, Fleisher D. Estimating Human Oral Fraction Dose Absorbed: A Correlation Using Rat Intestinal Membrane Permeability for Passive and Carrier-Mediated Compounds. Pharm Res. 1988;5(10):651–654.
- Puppolo MM, Hughey JR, Dillon T, Storey D, Jansen-Varnum S. Biomimetic Dissolution: A Tool to Predict Amorphous Solid Dispersion Performance. AAPS PharmSciTech. 2017;18(8):2841–2853.
- Puppolo MM, Hughey JR, Weber B, et al. Plasma modification of microporous polymer membranes for application in biomimetic dissolution studies. AAPS Open. 2017;3(9).
- Warnken Z, Puppolo M, Hughey J, Duarte I, Jansen-Varnum S. In Vitro–In Vivo Correlations of Carbamazepine Nanodispersions for Application in Formulation Development. J Pharm Sci. 2018;107(1):453–465.