Lipophilicity and hydrophobicity considerations in bio‐enabling oral formulations approaches – a PEARRL review

This review highlights aspects of drug hydrophobicity and lipophilicity as determinants of different oral formulation approaches with specific focus on enabling formulation technologies. An overview is provided on appropriate formulation selection by focussing on the physicochemical properties of the drug.

[1]  Haiyan Li,et al.  Structure-based in silico model profiles the binding constant of poorly soluble drugs with β-cyclodextrin. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[2]  K. Uekama,et al.  Cyclodextrins in drug carrier systems. , 1987, Critical reviews in therapeutic drug carrier systems.

[3]  Woldeamanuel A. Birru,et al.  Computational Models of the Gastrointestinal Environment. 1. The Effect of Digestion on the Phase Behavior of Intestinal Fluids. , 2017, Molecular pharmaceutics.

[4]  Christel A. S. Bergström,et al.  Computational Prediction of Drug Solubility in Lipid Based Formulation Excipients , 2013, Pharmaceutical Research.

[5]  Christel A. S. Bergström,et al.  The Need for Restructuring the Disordered Science of Amorphous Drug Formulations , 2017, Pharmaceutical Research.

[6]  Inayet Dumanli.  MECHANISTIC STUDIES TO ELUCIDATE THE ROLE OF LIPID VEHICLES ON SOLUBILITY, FORMULATION AND BIOA VAILABILITY OF POORLY SOLUBLE COMPOUNDS , 2002 .

[7]  T. Higuchi,et al.  Rate of release of medicaments from ointment bases containing drugs in suspension. , 1961, Journal of pharmaceutical sciences.

[8]  Navnit H. Shah,et al.  Structured Development Approach for Amorphous Systems , 2012 .

[9]  Christopher J. H. Porter,et al.  Computational prediction of formulation strategies for beyond-rule-of-5 compounds. , 2016, Advanced drug delivery reviews.

[10]  R Holm,et al.  Supersaturated Self-Nanoemulsifying Drug Delivery Systems (super-SNEDDS) , 2012 .

[11]  G. Mul,et al.  Evaluation of Mesoporous TCPSi, MCM-41, SBA-15, and TUD-1 Materials as API Carriers for Oral Drug Delivery , 2007, Drug delivery.

[12]  S. Yalkowsky,et al.  Estimation of the aqueous solubility I: application to organic nonelectrolytes. , 2001, Journal of pharmaceutical sciences.

[13]  M. Sillanpää,et al.  Utilization of agro-industrial and municipal waste materials as potential adsorbents for water treatment—A review , 2010 .

[14]  M. Hussain,et al.  Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction , 2016, Pharmaceutical Research.

[15]  Bruno C. Hancock,et al.  Molecular mobility of amorphous pharmaceuticals determined using differential scanning calorimetry , 2001 .

[16]  H. Santos,et al.  Drug delivery formulations of ordered and nonordered mesoporous silica: comparison of three drug loading methods. , 2011, Journal of pharmaceutical sciences.

[17]  Peter L D Wildfong,et al.  The Application of Modeling and Prediction to the Formation and Stability of Amorphous Solid Dispersions. , 2018, Journal of pharmaceutical sciences.

[18]  J-Y Choi,et al.  Characteristics of polymers enabling nano-comminution of water-insoluble drugs. , 2008, International journal of pharmaceutics.

[19]  C. Porter,et al.  Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs , 2007, Nature Reviews Drug Discovery.

[20]  Gustaf Arrhenius,et al.  X-ray diffraction procedures for polycrystalline and amorphous materials , 1955 .

[21]  Thomas Rades,et al.  Supersaturated Self-Nanoemulsifying Drug Delivery Systems (Super-SNEDDS) Enhance the Bioavailability of the Poorly Water-Soluble Drug Simvastatin in Dogs , 2012, The AAPS Journal.

[22]  B. Griffin,et al.  Mesoporous silica‐based dosage forms improve bioavailability of poorly soluble drugs in pigs: case example fenofibrate , 2017, The Journal of pharmacy and pharmacology.

[23]  Rajeswari Challa,et al.  Cyclodextrins in drug delivery: An updated review , 2005, AAPS PharmSciTech.

[24]  Martin Kuentz,et al.  Rapid determination of drug solubilization versus supersaturation in natural and digested lipids. , 2016, International journal of pharmaceutics.

[25]  Anette Müllertz,et al.  Lipid-based Formulations for Danazol Containing a Digestible Surfactant, Labrafil M2125CS: In Vivo Bioavailability and Dynamic In Vitro Lipolysis , 2008, Pharmaceutical Research.

[26]  Christel A. S. Bergström,et al.  Poorly soluble marketed drugs display solvation limited solubility. , 2007, Journal of medicinal chemistry.

[27]  Jean-Marie Devoisselle,et al.  Solid-State NMR Study of Ibuprofen Confined in MCM-41 Material , 2006 .

[28]  D. Hauss.  Oral lipid-based formulations. , 2007, Advanced drug delivery reviews.

[29]  R. Holm,et al.  Aqueous solubility: simple predictive methods (in silico, in vitro and bio-relevant approaches). , 2013, International journal of pharmaceutics.

[30]  V. Stella,et al.  Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery. , 1996, Journal of pharmaceutical sciences.

[31]  A. Bansal,et al.  Physical stability and solubility advantage from amorphous celecoxib: the role of thermodynamic quantities and molecular mobility. , 2004, Molecular pharmaceutics.

[32]  Christel A. S. Bergström,et al.  Contribution of solid-state properties to the aqueous solubility of drugs. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[33]  María Vallet-Regí,et al.  Ordered mesoporous materials in the context of drug delivery systems and bone tissue engineering. , 2006, Chemistry.

[34]  Guilan Quan,et al.  Loading amorphous Asarone in mesoporous silica SBA-15 through supercritical carbon dioxide technology to enhance dissolution and bioavailability. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[35]  R. Müller,et al.  Oral hesperidin-Amorphization and improved dissolution properties by controlled loading onto porous silica. , 2017, International journal of pharmaceutics.

[36]  R. Williams,et al.  Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection , 2017, Drug development and industrial pharmacy.

[37]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings , 1997 .

[38]  C. Pouton,et al.  Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[39]  Martin Kuentz,et al.  Biorelevant Drug Solubility Enhancement Modeled by a Linear Solvation Energy Relationship. , 2018, Journal of pharmaceutical sciences.

[40]  Joseph L. Kanig,et al.  Increasing Dissolution Rates and Gastrointestinal Absorption of Drugs via Solid Solutions and Eutectic mixtures III: Experimental Evaluation of Griseofulvin—succinic Acid Solid Solution , 1966 .

[41]  D. Hauss,et al.  Oral lipid-based formulations : enhancing the bioavailability of poorly water-soluable drugs , 2007 .

[42]  Anette Müllertz,et al.  Lipid-based formulations for oral administration of poorly water-soluble drugs. , 2013, International journal of pharmaceutics.

[43]  Barrett E. Rabinow,et al.  Nanosuspensions in drug delivery , 2004, Nature Reviews Drug Discovery.

[44]  Amrit Paudel,et al.  Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. , 2013, International journal of pharmaceutics.

[45]  C. Pouton,et al.  Transformation of Biopharmaceutical Classification System Class I and III Drugs Into Ionic Liquids and Lipophilic Salts for Enhanced Developability Using Lipid Formulations. , 2018, Journal of Pharmacy and Science.

[46]  Joel H. Hildebrand,et al.  The solubility of nonelectrolytes , 1964 .

[47]  Jinming Gao,et al.  Nanonization strategies for poorly water-soluble drugs. , 2011, Drug discovery today.

[48]  Å. Rasmuson,et al.  Determination of the activity of a molecular solute in saturated solution , 2008 .

[49]  M. Vallet‐Regí,et al.  Drug confinement and delivery in ceramic implants. , 2007, Drug metabolism letters.

[50]  R. Majors.  High-performance liquid chromatography on small particle silica gel. , 1972, Analytical chemistry.

[51]  Shaobin Wang,et al.  Ordered mesoporous materials for drug delivery , 2009 .

[52]  M. Chehimi,et al.  Triazole/Triazine-Functionalized Mesoporous Silica As a Hybrid Material Support for Palladium Nanocatalyst. , 2017, Langmuir.

[53]  David Malik,et al.  Cyclodextrin knowledgebase a web-based service managing CD-ligand complexation data , 2010, J. Comput. Aided Mol. Des..

[54]  B. Bugarski,et al.  Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[55]  J. Vermant,et al.  Formulate-ability of ten compounds with different physicochemical profiles in SMEDDS. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[56]  R Atkin,et al.  Mechanism of cationic surfactant adsorption at the solid-aqueous interface. , 2003, Advances in colloid and interface science.

[57]  S. Gurunath,et al.  Amorphous solid dispersion method for improving oral bioavailability of poorly water-soluble drugs , 2013 .

[58]  V. Lehto,et al.  Mesoporous systems for poorly soluble drugs. , 2013, International journal of pharmaceutics.

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

[60]  C. Barbé,et al.  Silica Particles: A Novel Drug‐Delivery System , 2004 .

[61]  Anoop Kumar,et al.  Lipophilic salts of poorly soluble compounds to enable high‐dose lipidic SEDDS formulations in drug discovery , 2017, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[62]  J. Martens,et al.  Potential of ordered mesoporous silica for oral delivery of poorly soluble drugs. , 2011, Therapeutic delivery.

[63]  J Dressman,et al.  Improving drug solubility for oral delivery using solid dispersions. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[64]  M. Senna,et al.  Solid State Radical Recombination and Charge Transfer across the Boundary between Indomethacin and Silica under Mechanical Stress , 2002 .

[65]  Shudong Wang,et al.  Lipophilic Prodrugs of SN38: Synthesis and in Vitro Characterization toward Oral Chemotherapy. , 2016, Molecular pharmaceutics.

[66]  C. Porter,et al.  Effect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats. , 2000, Journal of pharmaceutical sciences.

[67]  Colin W Pouton,et al.  Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[68]  W. L. Bragg,et al.  2 – The Diffraction of Short Electromagnetic Waves by a Crystal* , 1913 .

[69]  T. Sainio,et al.  Thermodynamics of tetracycline adsorption on silica , 2007 .

[70]  R. Pinal,et al.  Development of novel microprecipitated bulk powder (MBP) technology for manufacturing stable amorphous formulations of poorly soluble drugs. , 2012, International journal of pharmaceutics.

[71]  He Hui,et al.  Oxidized mesoporous silicon microparticles for improved oral delivery of poorly soluble drugs. , 2010, Molecular pharmaceutics.

[72]  R. Bogner,et al.  Spontaneous crystalline-to-amorphous phase transformation of organic or medicinal compounds in the presence of porous media, part 1: thermodynamics of spontaneous amorphization. , 2011, Journal of pharmaceutical sciences.

[73]  Hywel D Williams,et al.  Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid based formulations. , 2015, Molecular pharmaceutics.

[74]  Christel A.S. Bergström,et al.  Early drug development predictions of glass-forming ability and physical stability of drugs. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[75]  M. K. Lee,et al.  Hydrophilic and hydrophobic amino acid copolymers for nano-comminution of poorly soluble drugs. , 2010, International journal of pharmaceutics.

[76]  Patrick Augustijns,et al.  Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[77]  Hywel D Williams,et al.  Strategies to Address Low Drug Solubility in Discovery and Development , 2013, Pharmacological Reviews.

[78]  A. Crean,et al.  Mesoporous silica formulation strategies for drug dissolution enhancement: a review , 2016, Expert opinion on drug delivery.

[79]  Harsh Chauhan,et al.  Classification of solid dispersions: correlation to (i) stability and solubility (ii) preparation and characterization techniques , 2015, Drug development and industrial pharmacy.

[80]  K. Uekama,et al.  Design and evaluation of cyclodextrin-based drug formulation. , 2004, Chemical & pharmaceutical bulletin.

[81]  Patrick Augustijns,et al.  Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. , 2008, International journal of pharmaceutics.

[82]  D. J. Price,et al.  Enhanced oral delivery of celecoxib via the development of a supersaturable amorphous formulation utilising mesoporous silica and co-loaded HPMCAS. , 2016, International journal of pharmaceutics.

[83]  Christopher J. H. Porter,et al.  Tools for Early Prediction of Drug Loading in Lipid-Based Formulations , 2015, Molecular pharmaceutics.

[84]  J. Humbeeck,et al.  Aging behavior of pharmaceutical formulations of itraconazole on SBA-15 ordered mesoporous silica carrier material , 2010 .

[85]  E. Wasan,et al.  Review and analysis of FDA approved drugs using lipid-based formulations , 2017, Drug development and industrial pharmacy.

[86]  Mark E. Davis,et al.  Cyclodextrin-based pharmaceutics: past, present and future , 2004, Nature Reviews Drug Discovery.

[87]  J. S. Beck,et al.  Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism , 1992, Nature.

[88]  Thorsteinn Loftsson,et al.  Cyclodextrins as functional excipients: methods to enhance complexation efficiency. , 2012, Journal of pharmaceutical sciences.

[89]  M. Andersson,et al.  Solvent strategies for loading and release in mesoporous silica , 2014 .

[90]  J. Dressman,et al.  Mesoporous silica‐based dosage forms improve release characteristics of poorly soluble drugs: case example fenofibrate , 2016, The Journal of pharmacy and pharmacology.

[91]  Nicholas A Peppas,et al.  Higuchi equation: derivation, applications, use and misuse. , 2011, International journal of pharmaceutics.

[92]  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 .

[93]  S. Al-Nimry,et al.  Stabilization and Amorphization of Lovastatin Using Different Types of Silica , 2017, AAPS PharmSciTech.

[94]  L. Miller,et al.  The utility of cyclodextrins for enhancing oral bioavailability. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[95]  Jianlin Shi,et al.  Uniform Rattle‐type Hollow Magnetic Mesoporous Spheres as Drug Delivery Carriers and their Sustained‐Release Property , 2008 .

[96]  Bradley D Anderson,et al.  What determines drug solubility in lipid vehicles: is it predictable? , 2008, Advanced drug delivery reviews.

[97]  Bernard Van Eerdenbrugh,et al.  A classification system to assess the crystallization tendency of organic molecules from undercooled melts. , 2010, Journal of pharmaceutical sciences.

[98]  P. Breen,et al.  Cyclodextrins in pharmaceutical formulations II: solubilization, binding constant, and complexation efficiency. , 2016, Drug discovery today.

[99]  Venkata Raman Kallakunta,et al.  Melt extrusion with poorly soluble drugs - An integrated review. , 2018, International journal of pharmaceutics.

[100]  W. Saenger,et al.  Flip‐Flop Hydrogen Bonds in β‐Cyclodextrin—A Generally Valid Principle in Polysaccharides? , 1983 .

[101]  S. Qi,et al.  Microstructure of an immiscible polymer blend and its stabilization effect on amorphous solid dispersions. , 2013, Molecular pharmaceutics.

[102]  K. Gubbins,et al.  Freezing behavior in porous glasses and MCM-41 , 2001 .

[103]  D. T. Friesen,et al.  Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview. , 2008, Molecular pharmaceutics.

[104]  Thorsteinn Loftsson,et al.  Cyclodextrins as pharmaceutical solubilizers. , 2007, Advanced drug delivery reviews.

[105]  Indrajit Ghosh,et al.  Identifying the correlation between drug/stabilizer properties and critical quality attributes (CQAs) of nanosuspension formulation prepared by wet media milling technology. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[106]  M. B. James,et al.  Preparation of glass solutions of three poorly water soluble drugs by spray drying, melt extrusion and ball milling. , 2007, International journal of pharmaceutics.

[107]  P. Constantinides,et al.  Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (P-gp) substrate drugs: in vitro/in vivo case studies. , 2007, Journal of pharmaceutical sciences.

[108]  H. Santos,et al.  Comparison of mesoporous silicon and non-ordered mesoporous silica materials as drug carriers for itraconazole. , 2011, International journal of pharmaceutics.

[109]  Joseph L. Kanig,et al.  Increasing Dissolution Rates and Gastrointestinal Absorption of Drugs via solid Solutions and Eutectic mixtures II: Experimental Evaluation of a Eutectic Mixture: Urea-acetaminophen System , 1966 .

[110]  J. Salonen,et al.  Mesoporous silicon in drug delivery applications. , 2008, Journal of pharmaceutical sciences.

[111]  Martin Kuentz,et al.  Theoretical Considerations of the Prigogine-Defay Ratio with Regard to the Glass-Forming Ability of Drugs from Undercooled Melts. , 2016, Molecular pharmaceutics.

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

[113]  Å. Rasmuson,et al.  Prediction of solubility curves and melting properties of organic and pharmaceutical compounds. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[114]  M. Abraham,et al.  The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship. , 1999, Journal of pharmaceutical sciences.

[115]  V. Stella,et al.  Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[116]  D O Thompson,et al.  Cyclodextrins--enabling excipients: their present and future use in pharmaceuticals. , 1997, Critical reviews in therapeutic drug carrier systems.

[117]  O. Almarsson,et al.  Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. , 2007, Journal of pharmaceutical sciences.

[118]  J. Szejtli,et al.  Medicinal Applications of Cyclodextrins , 1994, Medicinal research reviews.

[119]  Christel A. S. Bergström,et al.  Physical stability of drugs after storage above and below the glass transition temperature: Relationship to glass-forming ability , 2015, International journal of pharmaceutics.

[120]  E. Monflier.  cyclodextrins , 2020, Catalysis from A to Z.

[121]  M. Brewster,et al.  Role of cyclodextrins in improving oral drug delivery , 2004 .

[122]  P. Amin,et al.  Solubility modulation of bicalutamide using porous silica , 2013, Journal of Pharmaceutical Investigation.

[123]  A. Maliniak,et al.  Molecular Properties Related to the Anomalous Solubility of β-Cyclodextrin , 2004 .

[124]  Arik Dahan,et al.  The effect of different lipid based formulations on the oral absorption of lipophilic drugs: the ability of in vitro lipolysis and consecutive ex vivo intestinal permeability data to predict in vivo bioavailability in rats. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[125]  Thomas Rades,et al.  In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate , 2014, The AAPS Journal.

[126]  Elaine Merisko-Liversidge,et al.  Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. , 2011, Advanced drug delivery reviews.

[127]  Bruno C. Hancock,et al.  What is the True Solubility Advantage for Amorphous Pharmaceuticals? , 2000, Pharmaceutical Research.

[128]  Martin Kuentz,et al.  In silico prediction of the solubility advantage for amorphous drugs - Are there property-based rules for drug discovery and early pharmaceutical development? , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[129]  Christel A. S. Bergström,et al.  Molecular characteristics for solid-state limited solubility. , 2008, Journal of medicinal chemistry.

[130]  M. Kuentz,et al.  Glass‐forming ability of compounds in marketed amorphous drug products , 2017, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[131]  Jennifer Dressman.  Oral Lipid-Based Formulations: Enhancing the Bioavailability of Poorly Water-Soluble Drugs , 2007 .

[132]  M. Vallet‐Regí,et al.  Influence of pore size of MCM-41 matrices on drug delivery rate , 2004 .

[133]  Christel A. S. Bergström,et al.  50years of oral lipid-based formulations: Provenance, progress and future perspectives. , 2016, Advanced drug delivery reviews.

[134]  Jenny Andersson,et al.  Influences of Material Characteristics on Ibuprofen Drug Loading and Release Profiles from Ordered Micro- and Mesoporous Silica Matrices , 2004 .

[135]  Beom-Jin Lee,et al.  Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[136]  D. Kalonia,et al.  Development of Improved Empirical Models for Estimating the Binding Constant of a β-Cyclodextrin Inclusion Complex , 2008, Pharmaceutical Research.

[137]  R. A. McGill,et al.  Determination of olive oil–gas and hexadecane–gas partition coefficients, and calculation of the corresponding olive oil–water and hexadecane–water partition coefficients , 1987 .