Prolonged drug release properties for orodispersible films by combining hot‐melt extrusion and solvent casting methods

Graphical abstract Figure. No caption available. &NA; Orodispersible films (ODFs) are an advantageous dosage form to accomplish patient convenience and compliance in oral drug delivery. They provide a number of special application features, such as the ease of administration without water and suitability for patients with swallowing problems. However, this promising dosage form has been limited to immediate release formulations so far. The aim of this study was to develop a thin film produced by solvent casting, which is rapidly disintegrating when placed in the mouth, but which provides prolonged drug release characteristics by incorporating drug‐loaded matrix particles (MPs). MPs were produced by hot‐melt extrusion and subsequent milling, using theophylline anhydrous as model drug and Eudragit® RS as matrix‐forming agent enabling prolonged drug release. ODFs were manufactured using hypromellose as film former. Dissolution studies were performed to investigate the kinetics and the duration of drug release. Additionally, disintegration time was determined using the PharmaTest® disintegration tester equipped with a specific sample holder for ODFs. All produced ODFs containing theophylline‐loaded MPs show fast disintegration while the drug release was prolonged. The degree of release prolongation increases with increasing sizes of incorporated MPs. Matrix‐controlled release kinetics were found for ODFs containing MPs with at least 315 &mgr;m in size. In summary, the production of fast disintegrating ODFs with prolonged release properties was feasible. Furthermore, freely adjustable dissolution profiles could be realized for ODFs by incorporating MPs of various particle sizes.

[1]  Yi Tsong,et al.  fDA Guidance for Industry 1 Dissolution Testing of Immediate Release Solid Oral Dosage Forms , 1997 .

[2]  Scott D. Barnhart Thin Film Oral Dosage Forms , 2008 .

[3]  M. Uhumwangho,et al.  In-vitro Characterization of Optimized Multi-Unit Dosage Forms of Theophylline and its Solid State Characterisation , 2011 .

[4]  L. Christrup,et al.  Patients' evaluation of shape, size and colour of solid dosage forms , 2001, Pharmacy World and Science.

[5]  Viridiana Arreola,et al.  Diagnosis and Management of Oropharyngeal Dysphagia and Its Nutritional and Respiratory Complications in the Elderly , 2010, Gastroenterology research and practice.

[6]  Eva Maria Hoffmann,et al.  Advances in orodispersible films for drug delivery , 2011, Expert opinion on drug delivery.

[7]  D. Levine,et al.  Dysphagia in patients with erosive esophagitis: prevalence, severity, and response to proton pump inhibitor treatment. , 2004, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[8]  H. Finestone,et al.  Rehabilitation medicine: 2. Diagnosis of dysphagia and its nutritional management for stroke patients. , 2003, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[9]  Jörg Breitkreutz,et al.  Oromucosal multilayer films for tailor-made, controlled drug delivery , 2017, Expert opinion on drug delivery.

[10]  Jörg Breitkreutz,et al.  Orodispersible drug formulations for children and elderly. , 2015, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[11]  Ana Filipa Borges,et al.  Oral films: Current status and future perspectives: I - Galenical development and quality attributes. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[12]  S. Simões,et al.  Oral films: Current status and future perspectives II - Intellectual property, technologies and market needs. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[13]  J. Cleary,et al.  Administration of crushed extended-release pentoxifylline tablets: bioavailability and adverse effects. , 1999, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[14]  S. Davis,et al.  Alimentary tract andpancreas Transit ofpharmaceutical dosage forms through the , 1986 .

[15]  B. Bloem,et al.  Prevalence of subjective dysphagia in community residents aged over 87. , 1990, BMJ.

[16]  Maren Preis,et al.  Oromucosal film preparations: points to consider for patient centricity and manufacturing processes , 2016, Expert opinion on drug delivery.

[17]  J. Virjee,et al.  The Effect of Size and Shape of Tablets on Their Esophageal Transit , 1986, Journal of clinical pharmacology.

[18]  J Breitkreutz,et al.  Swallowing dysfunction and dysphagia is an unrecognized challenge for oral drug therapy. , 2012, International journal of pharmaceutics.

[19]  J. Breitkreutz,et al.  Mechanical strength test for orodispersible and buccal films. , 2014, International journal of pharmaceutics.

[20]  N. Peppas,et al.  Mechanisms of solute release from porous hydrophilic polymers , 1983 .

[21]  Shaheen Hamdy,et al.  Acceptability of oral solid medicines in older adults with and without dysphagia: A nested pilot validation questionnaire based observational study. , 2016, International journal of pharmaceutics.

[22]  T. Nelms,et al.  Artificial hydration and nutrition in advanced Alzheimer's disease: facilitating family decision-making. , 2004, Journal of clinical nursing.

[23]  D. Wright,et al.  Medication administration in nursing homes. , 2002, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[24]  R. Suryanarayanan,et al.  Polymorphism in anhydrous theophylline--implications on the dissolution rate of theophylline tablets. , 1997, Journal of pharmaceutical sciences.

[25]  G. Dickens,et al.  Dose form modification – a common but potentially hazardous practice. A literature review and study of medication administration to older psychiatric inpatients , 2008, International Psychogeriatrics.