Effect of ionic strength and pH of dissolution media on theophylline release from hypromellose matrix tablets—Apparatus USP III, simulated fasted and fed conditions

Abstract The objectives of this study were to evaluate the effects of different media ionic concentration strengths and pH on the release of theophylline from a gel forming hydrophilic polymeric matrix. Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2–7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The ionic concentration strength of the media was varied over a range of 0–0.4 M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. Sodium chloride was used for ionic regulation due to its ability to salt out polymers in the midrange of the lyotropic series. The results showed that the ionic concentration strength had a profound effect on the drug release from the K100LV matrices. At pH 1.2 theophylline releases increased significantly within the first hour from 28% in water to 48% in the medium with ionic strength of 0.49 M. The K4M, K15M and K100M tablets, however, withstood the effects of media to the same extend at all ionic concentration strengths investigated. The similarity factor f2 was calculated using drug release in water as a reference. For the K100M matrices, f2 values of 74 (pH media), 80 (0.2 M media) and 72 (0.4 M media) suggested that it was the most resilient of all the matrices studied here. DSC hydration results explained the theophylline release from their HPMC matrices. Despite an increase in the percentage of bound water for the tablets made with high viscosity polymers K4M, K15M and K100M, they were, however, resilient to the ionic concentration strength effects as they were still able to form a strong gel layer. This methodology can be used as a valuable tool for predicting potential ionic effects related to in vivo fed and fasted states on drug release from hydrophilic ER matrices.

[1]  Ping I. Lee,et al.  Probing the Mechanisms of Drug Release from Hydroxypropylmethyl Cellulose Matrices , 1994, Pharmaceutical Research.

[2]  S. Hoag,et al.  Influence of methacrylic and acrylic acid polymers on the release performance of weakly basic drugs from sustained release hydrophilic matrices. , 2004, Journal of pharmaceutical sciences.

[3]  Sumio Watanabe,et al.  Water behavior during drug release from a matrix as observed using differential scanning calorimetry , 1995 .

[4]  H. Lennernäs,et al.  Characterization of Fluids from the Stomach and Proximal Jejunum in Men and Women , 1997, Pharmaceutical Research.

[5]  J D Andrade,et al.  Water and hydrogels. , 1973, Journal of biomedical materials research.

[6]  B. Lippold,et al.  Drug Release From Hydrocolloid Embeddings with High or Low Susceptibility to Hydrodynamic Stress , 1995, Pharmaceutical Research.

[7]  B. Abrahamsson,et al.  Evaluation of Solubilizers in the Drug Release Testing of Hydrophilic Matrix Extended-Release Tablets of Felodipine , 1994, Pharmaceutical Research.

[8]  Kristl Julijana,et al.  Analysis of surface properties of cellulose ethers and drug release from their matrix tablets. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[9]  N. L. Stemm,et al.  Qualitative evaluation of the mechanism of release of matrix sustained release dosage forms by measurement of polymer release , 1993 .

[10]  J. Sjögren,et al.  Investigation of prandial effects on hydrophilic matrix tablets. , 1999, Drug development and industrial pharmacy.

[11]  Paolo Colombo,et al.  Swelling-controlled release in hydrogel matrices for oral route , 1993 .

[12]  J. W. Moore,et al.  Mathematical comparison of dissolution profiles , 1996 .

[13]  S. Bolton,et al.  The influence of tablet density on the human oral absorption of sustained release acetaminophen matrix tablets , 1991 .

[14]  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.

[15]  S. B. Tiwari,et al.  Controlled release formulation of tramadol hydrochloride using hydrophilic and hydrophobic matrix system , 2008, AAPS PharmSciTech.

[16]  N A Peppas,et al.  Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). , 2001, Advanced drug delivery reviews.

[17]  Dissolution Technologies , 2022 .

[18]  John E. Hogan,et al.  The influence of additives on the cloud point, disintegration and dissolution of hydroxypropylmethylcellulose gels and matrix tablets , 1990 .

[19]  J. Dressman,et al.  Physiochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH. , 1997, Journal of pharmaceutical sciences.

[20]  M. Williams,et al.  Influence of ionic strength on matrix integrity and drug release from hydroxypropyl cellulose compacts , 1993 .

[21]  S. B. Tiwari,et al.  Extended-release oral drug delivery technologies: monolithic matrix systems. , 2008, Methods in molecular biology.

[22]  Martyn C. Davies,et al.  Structure and behaviour in hydrophilic matrix sustained release dosage forms: 3. The influence of pH on the sustained-release performance and internal gel structure of sodium alginate matrices , 1995 .

[23]  Ali R. Rajabi-Siahboomi,et al.  A study on the interaction of water and cellulose ethers using differential scanning calorimetry , 1997 .

[24]  S. Yoshioka,et al.  Effect of Water Mobility on Drug Hydrolysis Rates in Gelatin Gels , 1992, Pharmaceutical Research.

[25]  J. Schwartz,et al.  Theophylline controlled-release formulations: in vivo-in vitro correlations. , 1996, Biopharmaceutics & drug disposition.

[26]  P. Heng,et al.  Matrix swelling: A simple model describing extent of swelling of HPMC matrices , 1995 .

[27]  J. Siepmann,et al.  pH-independent release of a weakly basic drug from water-insoluble and -soluble matrix tablets. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[28]  James L. Ford,et al.  Thermal analysis of gels and matrix tablets containing cellulose ethers , 1995 .

[29]  Ken-ichi Yamamoto,et al.  Application of model-independent and model analysis for the investigation of effect of drug solubility on its release rate from hydroxypropyl methylcellulose sustained release tablets , 1996 .

[30]  Ali Nokhodchi,et al.  Study of dissolution hydrodynamic conditions versus drug release from hypromellose matrices: the influence of agitation sequence. , 2010, Colloids and surfaces. B, Biointerfaces.

[31]  S. Hoag,et al.  Microenvironmental pH modulation based release enhancement of a weakly basic drug from hydrophilic matrices. , 2006, Journal of pharmaceutical sciences.

[32]  J. Mcginity,et al.  Physical and enteric properties of soft gelatin capsules coated with eudragit ® L 30 D-55 , 1995 .

[33]  James A. Rogers,et al.  Studies on dissolution testing of the nifedipine gastrointestinal therapeutic system. I. Description of a two-phase in vitro dissolution test , 1997 .

[34]  O. Corrigan,et al.  Swelling and erosion properties of hydroxypropylmethylcellulose (Hypromellose) matrices--influence of agitation rate and dissolution medium composition. , 2004, International journal of pharmaceutics.

[35]  Matthew Roberts,et al.  The use of hypromellose in oral drug delivery , 2005, The Journal of pharmacy and pharmacology.

[36]  Mei-Ling Chen,et al.  Summary workshop report: biopharmaceutics classification system--implementation challenges and extension opportunities. , 2004, Journal of pharmaceutical sciences.

[37]  Carla Caramella,et al.  Influence of medium on dissolution-erosion behaviour of Na carboxymethylcellulose and on viscoelastic properties of gels , 1995 .