Investigation of dissolution behavior of diclofenac sodium extended release formulations under standard and biorelevant test conditions

Background: Dissolution characteristics of four extended release (ER) generic formulations of diclofenac sodium were examined. Aim: The aim of this study was to compare the drug dissolution behavior of diclofenac ER generics to clarify whether the products are characterized by comparable dissolution characteristics under the applied test conditions. Methods: The investigations were performed in the USP apparatus 2 and in the new biorelevant dissolution stress test device. Results: The experiments yielded striking differences between the generic formulations. Applying USP apparatus 2 it was noticed that the dissolution profiles of the products were distinctly affected by the stirring rate. Using the biorelevant dissolution stress test device susceptibility of the products to biorelevant stresses was observed. Change of pH within the experiments reduced the dissolution rates of all formulations and distinctly influenced their dissolution characteristics. Conclusion: The study demonstrates clearly the divergences in the dissolution behavior among the generic ER formulations of diclofenac sodium. The observed susceptibility of the tested dosage forms toward biorelevant stress bears in our interpretation the risk to cause unwanted fluctuations in drug plasma concentration profiles.

[1]  N. Hosten,et al.  Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging , 2005, Alimentary pharmacology & therapeutics.

[2]  R. Small,et al.  Diclofenac sodium. , 2020, Clinical pharmacy.

[3]  J. Hardcastle,et al.  Measurement of gastrointestinal pH profiles in normal ambulant human subjects. , 1988, Gut.

[4]  L Trahms,et al.  Magnetic marker monitoring of disintegrating capsules. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[5]  J. Dressman,et al.  Dissolution Media Simulating Conditions in the Proximal Human Gastrointestinal Tract: An Update , 2008, Pharmaceutical Research.

[6]  D. Barends,et al.  Biowaiver monographs for immediate release solid oral dosage forms: diclofenac sodium and diclofenac potassium. , 2009, Journal of pharmaceutical sciences.

[7]  Clive G. Wilson,et al.  Irregular absorption profiles observed from diclofenac extended release tablets can be predicted using a dissolution test apparatus that mimics in vivo physical stresses. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[8]  I. Beck,et al.  Determination of transit time in the human jejunum by the single-injection indicator-dilution technic , 1968, The American Journal of Digestive Diseases.

[9]  James C. Sexton,et al.  Computational fluid dynamics modeling of the paddle dissolution apparatus: Agitation rate, mixing patterns, and fluid velocities , 2004, AAPS PharmSciTech.

[10]  T. Zoeller,et al.  Simplified Biorelevant Media for Screening Dissolution Performance of Poorly Soluble Drugs , 2007 .

[11]  P. Armenante,et al.  Hydrodynamic, mass transfer, and dissolution effects induced by tablet location during dissolution testing. , 2009, Journal of pharmaceutical sciences.

[12]  C H Liu,et al.  In‐vitro and In‐vivo Studies of the Diclofenac Sodium Controlled‐release Matrix Tablets , 1995, The Journal of pharmacy and pharmacology.

[13]  P. Bampton,et al.  Basal pressure patterns and reflexive motor responses in the human ileocolonic junction. , 1999, American journal of physiology. Gastrointestinal and liver physiology.

[14]  M. Rongier,et al.  Evaluation of the gastric absorption and emptying of drugs under various pH conditions using a simple intubation method: application to diclofenac. , 1989, British journal of clinical pharmacology.

[15]  V. Pillay,et al.  Evaluation and comparison of dissolution data derived from different modified release dosage forms: an alternative method. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Jonathan M Goodman,et al.  Diclofenac solubility: independent determination of the intrinsic solubility of three crystal forms. , 2007, Journal of medicinal chemistry.

[17]  Y. Seta,et al.  A unique dosage form to evaluate the mechanical destructive force in the gastrointestinal tract. , 2000, International journal of pharmaceutics.

[18]  Peter Meredith,et al.  Bioequivalence and other unresolved issues in generic drug substitution. , 2003, Clinical therapeutics.

[19]  O. Corrigan,et al.  Preparation and characterisation of a range of diclofenac salts. , 2001, International journal of pharmaceutics.

[20]  R. Fisher,et al.  Gastric emptying of a non‐digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy , 2008, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[21]  J. D. Henderson,et al.  Generic substitution: issues for problematic drugs. , 2001, Southern medical journal.

[22]  R. N. Brogden,et al.  Diclofenac Sodium: A Review of its Pharmacological Properties and Therapeutic Use in Rheumatic Diseases and Pain of Varying Origin , 1980, Drugs.

[23]  L. Valvo,et al.  Diclofenac sodium multisource prolonged release tablets--a comparative study on the dissolution profiles. , 2005, Journal of pharmaceutical and biomedical analysis.

[24]  V. John,et al.  Application of Radiotelemetric Technique in Evaluating Diclofenac Sodium Absorption After Oral Administration of Various Dosage Forms in Healthy Volunteers , 1990, Pharmaceutical Research.

[25]  Lutz Trahms,et al.  Magnetic Marker Monitoring: An application of biomagnetic measurement instrumentation and principles for the determination of the gastrointestinal behavior of magnetically marked solid dosage forms. , 2005, Advanced drug delivery reviews.

[26]  N A Peppas,et al.  Translocation of drug particles in HPMC matrix gel layer: effect of drug solubility and influence on release rate. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Paolo Colombo,et al.  Analysis of the swelling and release mechanisms from drug delivery systems with emphasis on drug solubility and water transport , 1996 .

[28]  H. Duthie.  Colonic response to eating. , 1978, Gastroenterology.

[29]  J. Lötsch,et al.  Population Pharmacokinetics of Fast Release Oral Diclofenac in Healthy Volunteers: Relation to Pharmacodynamics in an Experimental Pain Model , 2004, Pharmaceutical Research.

[30]  C. Liu,et al.  The development of matrix tablets for diclofenac sodium based on an empirical in vitro and in vivo correlation , 1997 .

[31]  C. Liu,et al.  Dissolution of diclofenac sodium from matrix tablets , 1992 .

[32]  G. Fazio,et al.  Factors governing the dissolution of diclofenac salts , 1996 .

[33]  J. Dressman,et al.  Characterization of the Human Upper Gastrointestinal Contents Under Conditions Simulating Bioavailability/Bioequivalence Studies , 2006, Pharmaceutical Research.

[34]  I. Tucker,et al.  Matrix formation in sustained release tablets: possible mechanism of dose dumping. , 2003, International journal of pharmaceutics.