Effect of Molecular Weight on the Dissolution Profiles of PEG Solid Dispersions Containing Ketoprofen

Solid dispersions are typically binary systems with a hydrophilic matrix polymer and a lipophilic active substance. During formulation, the drug undergoes a crystalline to amorphous phase transition, which leads to a supersaturated solution providing enhanced bioavailability. The interaction of the active substance and the polymer is unique and influences the level of supersaturation. We aimed to investigate the relationship between low molecular weight polyethylene glycol derivates PEG 1000, 1500, and 2000 and ketoprofen regarding the effect of molecular weight. The physicochemical properties of solid dispersions prepared with hot melt homogenization and their respective physical mixtures were investigated with Fourier transform infrared spectroscopy, powder X-ray diffraction and scanning electron microscopy techniques. A phase solubility study was carried out in hydrochloric acid media which showed no difference between the three polymers, but the dissolution curves differed considerably. PEG 1000 had higher percentage of released drug than PEG 1500 and 2000, which had similar results. These results indicate that when multiple low molecular weight PEGs are suitable as matrix polymers of solid dispersions, the molecular weight has only limited impact on physicochemical characteristics and interactions and further investigation is needed to select the most applicable candidate.

[1]  B. Hens,et al.  Challenges and Strategies for Solubility Measurements and Dissolution Method Development for Amorphous Solid Dispersion Formulations , 2022, The AAPS Journal.

[2]  N. Passerini,et al.  Investigating the physicochemical properties of solid dispersions based on semicrystalline carriers: a case study with ketoprofen. , 2022, International journal of pharmaceutics.

[3]  W. Stagner,et al.  Optimized L-SNEDDS and spray-dried S-SNEDDS using a linked QbD-DM3 rational design for model compound ketoprofen. , 2022, International journal of pharmaceutics.

[4]  T. Tagami,et al.  Contamination-Free Milling of Ketoprofen Nanoparticles Using Mannitol Medium and Hoover Automatic Muller: Optimization of Effective Design of Experiment. , 2022, Biological & pharmaceutical bulletin.

[5]  Xing Tang,et al.  A comparative study on in vitro and in vivo characteristics of enzalutamide nanocrystals versus amorphous solid dispersions and a better prediction for bioavailability based on "spring-parachute" model. , 2022, International journal of pharmaceutics.

[6]  P. Nukala,et al.  Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization , 2022, Pharmaceutics.

[7]  M. Gorenflo,et al.  Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years , 2022, Pediatric Drugs.

[8]  É. Fenyvesi,et al.  Investigation of the Drug Carrier Properties of Insoluble Cyclodextrin Polymer Microspheres , 2022, Biomolecules.

[9]  M. Bagnasco,et al.  Ketoprofen lysine salt has a better gastrointestinal and renal tolerability than ketoprofen acid: A comparative tolerability study in the Beagle dog. , 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[10]  S. Shah,et al.  Solid dispersion technology as a formulation strategy for the fabrication of modified release dosage forms: A comprehensive review , 2022, DARU Journal of Pharmaceutical Sciences.

[11]  B. Nieradko-Iwanicka,et al.  The comparison of dexketoprofen and other painkilling medications (review from 2018 to 2021). , 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[12]  Ruochen Yang,et al.  Phase separation in surfactant-containing amorphous solid dispersions: orthogonal analytical methods to probe the effects of surfactants on morphology and phase composition. , 2022, International journal of pharmaceutics.

[13]  Tulsi Sagar Sheth,et al.  Optimizing similarity factor of in vitro drug release profile for development of early stage formulation of drug using linear regression model , 2021 .

[14]  A. Paradkar,et al.  Aqueous and pH dependent coacervation method for taste masking of paracetamol via amorphous solid dispersion formation , 2021, Scientific Reports.

[15]  P. Sarzi-Puttini,et al.  Comparison of Efficacy of Ketoprofen and Ibuprofen in Treating Pain in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis , 2021, Pain and Therapy.

[16]  Selma Škrbo,et al.  In vitro pH dependent passive transport of ketoprofen and metformin , 2020, ADMET & DMPK.

[17]  Madhabi Lata Shuma,et al.  Impact of drying on dissolution behavior of carvedilol-loaded sustained release solid dispersion: development and characterization , 2020, Heliyon.

[18]  Yanhua Li,et al.  Albendazole solid dispersions prepared using PEG6000 and Poloxamer188: formulation, characterization and in vivo evaluation , 2020, Pharmaceutical development and technology.

[19]  H. Lennernäs,et al.  Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat , 2020, Pharmaceutics.

[20]  Ritu Kaushik,et al.  An Overview on Recent Patents and Technologies on Solid Dispersion , 2020, Recent patents on drug delivery & formulation.

[21]  L. Fang,et al.  Transdermal enhancement strategy of ketoprofen and teriflunomide: the effect of enhanced drug-drug intermolecular interaction by permeation enhancer on drug release of compound transdermal patch. , 2019, International journal of pharmaceutics.

[22]  A. Healy,et al.  Amorphous solid dispersions of ketoprofen and poly-vinyl polymers prepared via electrospraying and spray drying: A comparison of particle characteristics and performance. , 2019, International journal of pharmaceutics.

[23]  P. Barbanti,et al.  Pharmacotherapy for acute migraines in children and adolescents , 2018, Expert opinion on pharmacotherapy.

[24]  G. Van den Mooter,et al.  The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers , 2016, Expert opinion on drug delivery.

[25]  H. Wen,et al.  Non-Sink Dissolution Conditions for Predicting Product Quality and In Vivo Performance of Supersaturating Drug Delivery Systems. , 2016, Journal of pharmaceutical sciences.

[26]  Siok-Yee Chan,et al.  The improved dissolution performance of a post processing treated spray-dried crystalline solid dispersion of poorly soluble drugs , 2016, Drug development and industrial pharmacy.

[27]  Bart Hens,et al.  Supersaturation and Precipitation of Posaconazole Upon Entry in the Upper Small Intestine in Humans. , 2015, Journal of pharmaceutical sciences.

[28]  N. H. Abu Kasim,et al.  Low-melting-point polymeric nanoshells for thermal-triggered drug release under hyperthermia condition , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[29]  S. Bandari,et al.  Development of ketoprofen loaded proliposomal powders for improved gastric absorption and gastric tolerance: in vitro and in situ evaluation , 2015, Pharmaceutical development and technology.

[30]  J. van Humbeeck,et al.  Crystallization Kinetics of Indomethacin/Polyethylene Glycol Dispersions Containing High Drug Loadings. , 2015, Molecular pharmaceutics.

[31]  L. S. Taylor,et al.  Phase separation kinetics in amorphous solid dispersions upon exposure to water. , 2015, Molecular pharmaceutics.

[32]  G. Amidon,et al.  The Biopharmaceutics Classification System: subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC. , 2014, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[33]  J. Sousa,et al.  In vitro release of ketoprofen from hydrophilic matrix tablets containing cellulose polymer mixtures , 2013, Drug development and industrial pharmacy.

[34]  Vikas Kumar,et al.  Physicochemical characterization and in vitro dissolution studies of solid dispersions of ketoprofen with PVP K30 and d-mannitol. , 2013, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[35]  S. Majumdar,et al.  Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology , 2012, AAPS PharmSciTech.

[36]  Michael T Harris,et al.  Modification of crystallization behavior in drug/polyethylene glycol solid dispersions. , 2012, Molecular pharmaceutics.

[37]  S. Surana,et al.  Solubility, dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique. , 2011, Chemical & pharmaceutical bulletin.

[38]  P. Sarzi-Puttini,et al.  Pain and ketoprofen: what is its role in clinical practice? , 2011, Reumatismo.

[39]  Sunil K. Jain,et al.  Development and in vitro evaluation of ibuprofen mouth dissolving tablets using solid dispersion technique. , 2010, Chemical & pharmaceutical bulletin.

[40]  A. Nada,et al.  Physicochemical characterization of gliclazide–macrogol solid dispersion and tablets based on optimized dispersion , 2010, Drug development and industrial pharmacy.

[41]  Prasanta Chowdhury,et al.  Kinetic modeling on drug release from controlled drug delivery systems. , 2010, Acta poloniae pharmaceutica.

[42]  S. Kyriacos,et al.  Modeling and Comparison of Dissolution Profiles of Diltiazem Modified-Release Formulations , 2009 .

[43]  Zeren Wang,et al.  Factors affecting the formation of eutectic solid dispersions and their dissolution behavior. , 2007, Journal of pharmaceutical sciences.

[44]  Y. Pei,et al.  Enhancing the Bioavailability of Cyclosporine A Using Solid Dispersion Containing Polyoxyethylene (40) Stearate , 2006, Drug development and industrial pharmacy.

[45]  M. L. González-Rodríguez,et al.  Characterization and Dissolution Properties of Ketoprofen in Binary and Ternary Solid Dispersions with Polyethylene Glycol and Surfactants , 2005, Drug development and industrial pharmacy.

[46]  J. Xiong,et al.  Solid state NMR perspective of drug-polymer solid solutions: a model system based on poly(ethylene oxide). , 2004, International journal of pharmaceutics.

[47]  D. Grant,et al.  Solid-state characterization of nifedipine solid dispersions. , 2002, International journal of pharmaceutics.

[48]  C. Goosen,et al.  The influence of the physicochemical characteristics and pharmacokinetic properties of selected NSAID's on their transdermal absorption. , 2000, International journal of pharmaceutics.

[49]  G. Trapani,et al.  Physicochemical characterization and in vivo properties of Zolpidem in solid dispersions with polyethylene glycol 4000 and 6000. , 1999, International journal of pharmaceutics.

[50]  P. Parrini,et al.  Thermal behavior and dissolution properties of naproxen from binary and ternary solid dispersions. , 1999, Drug development and industrial pharmacy.

[51]  M. L. García,et al.  An investigation of FB interactions with poly(ethylene glycol) 6000, poly(ethylene glycol) 4000, and poly-epsilon-caprolactone by thermoanalytical and spectroscopic methods and modeling. , 1998, Journal of pharmaceutical sciences.

[52]  M. H. Rubinstein,et al.  Physical Stability of Solid Dispersions Containing Triamterene or Temazepam in Polyethylene Glycols , 1997, The Journal of pharmacy and pharmacology.

[53]  G. Betageri,et al.  Enhancement of dissolution of glyburide by solid dispersion and lyophilization techniques , 1995 .

[54]  F. Otero-Espinar,et al.  The properties of solid dispersions of clofibrate in polyethylene glycols , 1995 .

[55]  C. Nyström,et al.  Physicochemical aspects of drug release. VI. Drug dissolution rate from solid particulate dispersions and the importance of carrier and drug particle properties , 1988 .

[56]  A. Serajuddin,et al.  Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drug from solid dispersions. , 1988, Journal of pharmaceutical sciences.

[57]  T. Kantor.  Ketoprofen: A Review of Its Pharmacologic and Clinical Properties , 1986, Pharmacotherapy.

[58]  J. Dubois,et al.  The properties of solid dispersions of indomethacin or phenylbutazone in polyethylene glycol , 1986 .

[59]  J. McGinty,et al.  Combined water-soluble carriers for coprecipitates of tolbutamide. , 1982, Journal of pharmaceutical sciences.

[60]  S. Riegelman,et al.  Pharmaceutical applications of solid dispersion systems. , 1971, Journal of pharmaceutical sciences.

[61]  S. Riegelman,et al.  Preparation and dissolution characteristics of several fast-release solid dispersions of griseofulvin. , 1969, Journal of pharmaceutical sciences.

[62]  Keiji Sekiguchi,et al.  Studies on Absorption of Eutectic Mixture. I. A Comparison of the Behavior of Eutectic Mixture of Sulfathiazole and that of Ordinary Sulfathiazole in Man. , 1961 .