155
Views
0
CrossRef citations to date
0
Altmetric
Review Article

Assessing and mitigating pH-mediated DDI risks in drug development – formulation approaches and clinical considerations

, , , , , & show all
Received 28 Nov 2023, Accepted 10 Apr 2024, Published online: 03 May 2024

References

  • Akimoto M, Nagahata N, Furuya A, Fukushima K, Higuchi S, Suwa T. 2000. Gastric pH profiles of beagle dogs and their use as an alternative to human testing. Eur J Pharm Biopharm. 49(2):99–102. doi: 10.1016/s0939-6411(99)00070-3.
  • Andersson T, Hassan-Alin M, Hasselgren G, Röhss K. 2001. Drug interaction studies with esomeprazole, the (s)-isomer of omeprazole. Clin Pharmacokinet. 40(7):523–537. doi: 10.2165/00003088-200140070-00004.
  • Babaei A, Bhargava V, Aalam S, Scadeng M, Mittal RK. 2009. Effect of proton pump inhibition on the gastric volume: assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 29(8):863–870. doi: 10.1111/j.1365-2036.2009.03947.x.
  • Badawy SI, Hussain MA. 2007. Microenvironmental pH modulation in solid dosage forms. J Pharm Sci. 96(5):948–959. doi: 10.1002/jps.20932.
  • Bavishi DD, Borkhataria CH. 2016. Spring and parachute: how cocrystals enhance solubility. Prog Cryst Growth Charact Mater. 62(3):1–8. doi: 10.1016/j.pcrysgrow.2016.07.001.
  • Bhalani DV, Nutan B, Kumar A, Singh Chandel AK. 2022. Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics. Biomedicines. 10(9):2055. doi: 10.3390/biomedicines10092055.
  • Bhujbal SV, Mitra B, Jain U, Gong Y, Agrawal A, Karki S, Taylor LS, Kumar S, Tony Zhou Q. 2021. Pharmaceutical amorphous solid dispersion: a review of manufacturing strategies. Acta Pharm Sin B. 11(8):2505–2536. doi: 10.1016/j.apsb.2021.05.014.
  • Blum RA, Shi H, Karol MD, Greski-Rose PA, Hunt RH. 1997. The comparative effects of lansoprazole, omeprazole, and ranitidine in suppressing gastric acid secretion. Clin Ther. 19(5):1013–1023. doi: 10.1016/s0149-2918(97)80053-7.
  • Bremmell KE, Prestidge CA. 2019. Enhancing oral bioavailability of poorly soluble drugs with mesoporous silica based systems: opportunities and challenges. Drug Dev Ind Pharm. 45(3):349–358. doi: 10.1080/03639045.2018.1542709.
  • Brooks S, Phelan MP, Chand B, Hatem S. 2009. Markedly elevated lipase as a clue to diagnosis of small bowel obstruction after gastric bypass. Am J Emerg Med. 27(9):1167.e5–1167.e7. doi: 10.1016/j.ajem.2008.12.004.
  • Cole S, Kerwash E, Andersson A. 2020. A summary of the current drug interaction guidance from the European Medicines Agency and considerations of future updates. Drug Metab Pharmacokinet. 35(1):2–11. doi: 10.1016/j.dmpk.2019.11.005.
  • Dajani EZ, Dajani NE, Shahwan TG. 2004. Over-the-counter drugs.
  • de Villiers MM. 1996. Influence of agglomeration of cohesive particles on the dissolution behaviour of furosemide powder. Int J Pharm. 136(1–2):175–179. doi: 10.1016/0378-5173(95)04380-2.
  • Del Re M, Omarini C, Diodati L, Palleschi M, Meattini I, Crucitta S, Lorenzini G, Isca C, Fontana A, Livi L, et al. 2021. Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients. ESMO Open. 6(5):100231. doi: 10.1016/j.esmoop.2021.100231.
  • Dodd S, Kollipara S, Sanchez-Felix M, Kim H, Meng Q, Beato S, Heimbach T. 2019. Prediction of ARA/PPI drug-drug interactions at the drug discovery and development interface. J Pharm Sci. 108(1):87–101. doi: 10.1016/j.xphs.2018.10.032.
  • Dong Z, Li J, Wu F, Zhao P, Lee S-C, Zhang L, Seo P, Zhang L. 2020. Application of physiologically‐based pharmacokinetic modeling to predict gastric pH‐dependent drug–drug interactions for weak base drugs. CPT Pharmacometrics Syst Pharmacol. 9(8):456–465. doi: 10.1002/psp4.12541.
  • Fadda HM, Hellström PM, Webb D-L. 2022. Intra-and inter-subject variability in gastric pH following a low-fat, low-calorie meal. Int J Pharm. 625:122069. doi: 10.1016/j.ijpharm.2022.122069.
  • FDA, U.S. 2005. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers.
  • FDA, U.S. 2020. Evaluation of gastric pH-dependent drug interactions with acid-reducing agents: study design, data analysis, and clinical implications. https://www.fda.gov/media/144026/download.
  • Gajewska M, Blumenstein L, Kourentas A, Mueller-Zsigmondy M, Lorenzo S, Sinn A, Velinova M, Heimbach T. 2020. Physiologically based pharmacokinetic modeling of oral absorption, pH, and food effect in healthy volunteers to drive alpelisib formulation selection. AAPS J. 22(6):134. doi: 10.1208/s12248-020-00511-7.
  • Garg V, Narang P, Taneja R. 2022. Antacids revisited: review on contemporary facts and relevance for self-management. J Int Med Res. 50(3):3000605221086457. doi: 10.1177/03000605221086457.
  • Giacomini KM, Huang S-M, Tweedie DJ, Benet LZ, Brouwe KLR, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM, et al. 2010. Membrane transporters in drug development. Nat Rev Drug Discov. 9 (3):215–236. doi: 10.1038/nrd3028.
  • Gigliobianco MR, Casadidio C, Censi R, Di Martino P. 2018. Nanocrystals of poorly soluble drugs: drug bioavailability and physicochemical stability. Pharmaceutics. 10(3):134. doi: 10.3390/pharmaceutics10030134.
  • Guo M, Sun X, Chen J, Cai T. 2021. Pharmaceutical cocrystals: a review of preparations, physicochemical properties and applications. Acta Pharm Sin B. 11(8):2537–2564. doi: 10.1016/j.apsb.2021.03.030.
  • Gupta D, Bhatia D, Dave V, Sutariya V, Varghese Gupta S. 2018. Salts of therapeutic agents: chemical, physicochemical, and biological considerations. Molecules. 23(7):1719. doi: 10.3390/molecules23071719.
  • Gutiérrez-Repiso C, Moreno-Indias I, Tinahones FJ. 2021. Shifts in gut microbiota and their metabolites induced by bariatric surgery. Impact of factors shaping gut microbiota on bariatric surgery outcomes. Rev Endocr Metab Disord. 22(4):1137–1156. doi: 10.1007/s11154-021-09676-8.
  • Hintz RJ, Johnson KC. 1989. The effect of particle size distribution on dissolution rate and oral absorption. Int J Pharm. 51(1):9–17. doi: 10.1016/0378-5173(89)90069-0.
  • IBRANCE® (palbociclib) capsules [prescribing information]. 2019. Pfizer Inc, New York, NY.
  • Ingersoll KS, Cohen J. 2008. The impact of medication regimen factors on adherence to chronic treatment: a review of literature. J Behav Med. 31(3):213–224. doi: 10.1007/s10865-007-9147-y.
  • Iwamoto T, Monma F, Ohishi K, Umino A, Suzuki K, Oka K, Kawakami K, Sekine T, Okuda M, Katayama N, et al. 2019. Evaluation of medication adherence and pharmacokinetics of dasatinib for earlier molecular response in Japanese patients with newly diagnosed chronic myeloid leukemia: a pilot study. Ther Drug Monit. 41(5):575–581. doi: 10.1097/FTD.0000000000000639.
  • Kambayashi A, Dressman JB. 2019. Predicting the changes in oral absorption of weak base drugs under elevated gastric pH using an in vitro–in silico–in vivo approach: case examples—dipyridamole, prasugrel, and nelfinavir. J Pharm Sci. 108(1):584–591. doi: 10.1016/j.xphs.2018.11.008.
  • Kesisoglou F, Mitra A. 2015. Application of absorption modeling in rational design of drug product under quality-by-design paradigm. AAPS J. 17(5):1224–1236. doi: 10.1208/s12248-015-9781-1.
  • Kesisoglou F, Panmai S, Wu Y. 2007. Nanosizing—Oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 59(7):631–644. doi: 10.1016/j.addr.2007.05.003.
  • Kesisoglou F, Vertzoni M, Reppas C. 2018. Physiologically based absorption modeling of salts of weak bases based on data in hypochlorhydric and achlorhydric biorelevant media. AAPS PharmSciTech. 19(7):2851–2858. doi: 10.1208/s12249-018-1059-3.
  • Kesisoglou F, Wu Y. 2008. Understanding the effect of API properties on bioavailability through absorption modeling. AAPS J. 10(4):516–525. doi: 10.1208/s12248-008-9061-4.
  • Kim S, Bilgili E, Davé RN. 2021. Impact of altered hydro­phobicity and reduced agglomeration on dissolution of micronized poorly water-soluble drug powders after dry coating. Int J Pharm. 606:120853. doi: 10.1016/j.ijpharm.2021.120853.
  • Kou D, Dwaraknath S, Fischer Y, Nguyen D, Kim M, Yiu H, Patel P, Ng T, Mao C, Durk M, et al. 2017. Biorelevant dissolution models for a weak base to facilitate formulation development and overcome reduced bioavailability caused by hypochlordyria or achlorhydria. Mol Pharm. 14(10):3577–3587. doi: 10.1021/acs.molpharmaceut.7b00593.
  • Kuminek G, Salehi N, Waltz NM, Sperry DC, Greenwood DE, Hate SS, Amidon GE. 2023. Use of gastrointestinal simulator, mass transport analysis, and absorption simulation to investigate the impact of pH modifiers in mitigating weakly basic drugs’ performance issues related to gastric ph: palbociclib case study. Mol Pharm. 20(1):147–158. doi: 10.1021/acs.molpharmaceut.2c00545.
  • Lahner E, Annibale B, Delle Fave G. 2009. Systematic review: impaired drug absorption related to the co-administration of antisecretory therapy. Aliment Pharmacol Ther. 29(12):1219–1229. doi: 10.1111/j.1365-2036.2009.03993.x.
  • Laine L, Hennekens C. 2010. Proton pump inhibitor and clopidogrel interaction: fact or fiction? Am J Gastroenterol. 105(1):34–41. doi: 10.1038/ajg.2009.638.
  • Lam LH, Capparelli EV, Kurzrock R. 2016. Association of concurrent acid-suppression therapy with survival outcomes and adverse event incidence in oncology patients receiving erlotinib. Cancer Chemother Pharmacol. 78(2):427–432. doi: 10.1007/s00280-016-3087-6.
  • Lau YY, Gu W, Lin T, Viraswami-Appanna K, Cai C, Scott JW, Shi M. 2017. Assessment of drug-drug interaction potential between ceritinib and proton pump inhibitors in healthy subjects and in patients with ALK-positive non-small cell lung cancer. Cancer Chemother Pharmacol. 79(6):1119–1128. doi: 10.1007/s00280-017-3308-7.
  • Levêque D, Becker G, Bilger K, Natarajan-Amé S. 2020. Clinical pharmacokinetics and pharmacodynamics of dasatinib. Clin Pharmacokinet. 59(7):849–856. doi: 10.1007/s40262-020-00872-4.
  • Lin W, Chen Y, Unadkat JD, Zhang X, Wu D, Heimbach T. 2022. Applications, challenges, and outlook for PBPK modeling and simulation: a regulatory, industrial and academic perspective. Pharm Res. 39(8):1701–1731. doi: 10.1007/s11095-022-03274-2.
  • Litou C, Vertzoni M, Goumas C, Vasdekis V, Xu W, Kesisoglou F, Reppas C. 2016. Characteristics of the human upper gastrointestinal contents in the fasted state under hypo- and a-chlorhydric gastric conditions under conditions of typical drug – drug interaction studies. Pharm Res. 33(6):1399–1412. doi: 10.1007/s11095-016-1882-8.
  • Litou C, Vertzoni M, Xu W, Kesisoglou F, Reppas C. 2017. The impact of reduced gastric acid secretion on dissolution of salts of weak bases in the fasted upper gastrointestinal lumen: data in biorelevant media and in human aspirates. Eur J Pharm Biopharm. 115:94–101. doi: 10.1016/j.ejpb.2017.02.009.
  • Liu J, Nagapudi K, Dolton MJ, Chiang P-C. 2021. Utilizing tiny-TIM to assess the effect of acid-reducing agents on the absorption of orally administered drugs. J Pharm Sci. 110(8):3020–3026. doi: 10.1016/j.xphs.2021.04.017.
  • Lu T, Fraczkiewicz G, Salphati L, Budha N, Dalziel G, Smelick GS, Morrissey KM, Davis JD, Jin JY, Ware JA, et al. 2017. Combining “bottom-up” and “top-down” approaches to assess the impact of food and gastric pH on Pictilisib (GDC-0941) pharmacokinetics. CPT Pharmacometrics Syst Pharmacol. 6(11):747–755. doi: 10.1002/psp4.12228.
  • Lui CY, Amidon GL, Berardi RR, Fleisher D, Youngberg C, Dressman JB. 1986. Comparison of gastrointestinal pH in dogs and humans: implications on the use of the beagle dog as a model for oral absorption in humans. J Pharm Sci. 75(3):271–274. doi: 10.1002/jps.2600750313.
  • Mahjour M, Kesisoglou F, Cruanes M, Xu W, Zhang D, Maguire TJ, Rosen LA, Templeton AC, Kress MH. 2014. Effect of added alkalizer and surfactant on dissolution and absorption of the potassium salt of a weakly basic poorly water‐soluble drug. J Pharm Sci. 103(6):1811–1818. doi: 10.1002/jps.23985.
  • Malik SN, Canaham DH, Gouda MW. 1975. Effect of surfactants on absorption through membranes III: effects of dioctyl sodium sulfosuccinate and poloxalene on absorption of a poorly absorbable drug, phenolsulfonphthalein, in rats. J Pharm Sci. 64(6):987–990. doi: 10.1002/jps.2600640620.
  • McConnell EL, Basit AW, Murdan S. 2008. Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments. J Pharm Pharmacol. 60(1):63–70. doi: 10.1211/jpp.60.1.0008.
  • Menning MM, Dalziel SM. 2013. Fumaric acid microenvironment tablet formulation and process development for crystalline cenicriviroc mesylate, a BCS IV compound. Mol Pharm. 10(11):4005–4015. doi: 10.1021/mp400286s.
  • Merisko-Liversidge E, Liversidge GG, Cooper ER. 2003. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 18(2):113–120. doi: 10.1016/s0928-0987(02)00251-8.
  • Miao L, Wu F, Yang X, Mousa YM, Ramamoorthy A, Lee S-C, Raines K, Zhang L, Seo P. 2022. Application of solubility and dissolution profile comparison for prediction of gastric pH-mediated drug-drug interactions. AAPS J. 24(1):35. doi: 10.1208/s12248-022-00684-3.
  • Miner PB, JR, Allgood LD, Grender JM. 2007. Comparison of gastric pH with omeprazole magnesium 20.6 mg (Prilosec OTC) o.m. famotidine 10 mg (Pepcid AC) b.d. and famotidine 20 mg b.d. over 14 days of treatment. Aliment Pharmacol Ther. 25(1):103–109. doi: 10.1111/j.1365-2036.2006.03129.x.
  • Mitra A, Kesisoglou F. 2013. Impaired drug absorption due to high stomach pH: a review of strategies for mitigation of such effect to enable pharmaceutical product development. Mol Pharm. 10(11):3970–3979. doi: 10.1021/mp400256h.
  • Mitra A, Kesisoglou F, Beauchamp M, Zhu W, Chiti F, Wu Y. 2011. Using absorption simulation and gastric pH modulated dog model for formulation development to overcome achlorhydria effect. Mol Pharm. 8(6):2216–2223. doi: 10.1021/mp200062a.
  • Mitra A, Parrott N, Miller N, Lloyd R, Tistaert C, Heimbach T, Ji Y, Kesisoglou F. 2020. Prediction of pH-dependent drug-drug interactions for basic drugs using physiologically based biopharmaceutics modeling: industry case studies. J Pharm Sci. 109(3):1380–1394. doi: 10.1016/j.xphs.2019.11.017.
  • Monschke M, Wagner KG. 2019. Amorphous solid dispersions of weak bases with pH-dependent soluble polymers to overcome limited bioavailability due to gastric pH variability – an in-vitro approach. Int J Pharm. 564:162–170. doi: 10.1016/j.ijpharm.2019.04.034.
  • Montenegro RC, Howarth A, Ceroni A, Fedele V, Farran B, Mesquita FP, Frejno M, Berger B-T, Heinzlmeir S, Sailem HZ, et al. 2020. Identification of molecular targets for the targeted treatment of gastric cancer using dasatinib. Oncotarget. 11(5):535–549. doi: 10.18632/oncotarget.27462.
  • Moseson DE, Corum ID, Lust A, Altman KJ, Hiew TN, Eren A, Nagy ZK, Taylor LS. 2021. Amorphous solid dispersions containing residual crystallinity: competition between dissolution and matrix crystallization. AAPS J. 23(4):69. doi: 10.1208/s12248-021-00598-6.
  • Moseson DE, Taylor LS. 2023. Crystallinity: a complex critical quality attribute of amorphous solid dispersions. Mol Pharm. 20(10):4802–4825. doi: 10.1021/acs.molpharmaceut.3c00526.
  • Nagar S, Radice C, Tuohy R, Stevens R, Bennyhoff D, Korzekwa K. 2023. The rat continuous intestine model predicts the impact of particle size and transporters on the oral absorption of glyburide. Mol Pharm. 20(1):219–231. doi: 10.1021/acs.molpharmaceut.2c00597.
  • Nagy J, Van Boxtel CJ, Koopmans RP, Kager PA, Schipper HG, Butter JJ. 2000. Effect of dose increase or cimetidine co-administration on albendazole bioavailability. Am J Tropical Med Hyg. 63(5):270–273. doi: 10.4269/ajtmh.2000.63.270.
  • Noyes AA, Whitney WR. 1897. The rate of solution of solid substances in their own solutions. J Am Chem Soc. 19(12):930–934. doi: 10.1021/ja02086a003.
  • O’Dwyer PJ, Litou C, Box KJ, Dressman JB, Kostewicz ES, Kuentz M, Reppas C. 2019. In vitro methods to assess drug precipitation in the fasted small intestine – a PEARRL review. J Pharm Pharmacol. 71(4):536–556. doi: 10.1111/jphp.12951.
  • Ogawa R, Echizen H. 2011. Clinically significant drug interactions with antacids: an update. Drugs. 71(14):1839–1864. doi: 10.2165/11593990-000000000-00000.
  • Pace F, et al. 2007. A review of rabeprazole in the treatment of acid-related diseases. Ther Clin Risk Manag. 3(3):363–379.
  • Pandi P, Bulusu R, Kommineni N, Khan W, Singh M. 2020. Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products. Int J Pharm. 586:119560. doi: 10.1016/j.ijpharm.2020.119560.
  • Pang J, Dalziel G, Dean B, Ware JA, Salphati L. 2013. Pharmacokinetics and absorption of the anticancer agents dasatinib and GDC-0941 under various gastric conditions in dogs – reversing the effect of elevated gastric pH with betaine HCl. Mol Pharm. 10(11):4024–4031. doi: 10.1021/mp400356m.
  • Parrott N, Stillhart C, Lindenberg M, Wagner B, Kowalski K, Guerini E, Djebli N, Meneses-Lorente G. 2020. PBPK modeling on food and gastric pH changes on the pharmacokinetics of entrectinib. AAPS J. 22(4):78. doi: 10.1208/s12248-020-00463-y.
  • Parrott NJ, Yu LJ, Takano R, Nakamura M, Morcos PN. 2016. Physiologically based absorption modeling to explore the impact of food and gastric pH changes on the pharmacokinetics of alectinib. AAPS J. 18(6):1464–1474. doi: 10.1208/s12248-016-9957-3.
  • Patel D, Bertz R, Ren S, Boulton DW, Någård M. 2020. A systematic review of gastric acid-reducing agent-mediated drug–drug interactions with orally administered medications. Clin Pharmacokinet. 59(4):447–462. doi: 10.1007/s40262-019-00844-3.
  • Patel S, Zhu W, Xia B, Sharma N, Hermans A, Ehrick JD, Kesisoglou F, Pennington J. 2019. Integration of precipitation kinetics from an in vitro, multicompartment transfer system and mechanistic oral absorption modeling for pharmacokinetic prediction of weakly basic drugs. J Pharm Sci. 108(1):574–583. doi: 10.1016/j.xphs.2018.10.051.
  • Prescott L. 1972. Mechanisms of renal excretion of drugs (with special reference to drugs used by anaesthetists). Br J Anaesth. 44(3):246–251. doi: 10.1093/bja/44.3.246.
  • Rao C, Li M, Sun X, Li M, Lian X, Wang H, Jia L, Niu B, Li W. 2020. Preparation and characterization of phosphate-stabilized amorphous calcium carbonate nanoparticles and their application in curcumin delivery. Mater Chem Phys. 255:123552. doi: 10.1016/j.matchemphys.2020.123552.
  • Salehi N, Kuminek G, Al-Gousous J, Sperry DC, Greenwood DE, Waltz NM, Amidon GL, Ziff RM, Amidon GE. 2021. Improving dissolution behavior and oral absorption of drugs with pH-dependent solubility using pH modifiers: a physiologically realistic mass transport analysis. Mol Pharm. 18(9):3326–3341. doi: 10.1021/acs.molpharmaceut.1c00262.
  • Saravana Kumar K, Prasanna Raju SM. 2013. Y dissolution enhancement of poorly soluble drugs by using complexation technique – a review. J. Pharm. Sci. Res. 5(5):120–124.
  • Schittny A, Philipp-Bauer S, Detampel P, Huwyler J, Puchkov M. 2020. Mechanistic insights into effect of surfactants on oral bioavailability of amorphous solid dispersions. J Control Release. 320:214–225. doi: 10.1016/j.jconrel.2020.01.031.
  • Schöller-Gyüre M, Kakuda TN, De Smedt G, Vanaken H, Bouche M-P, Peeters M, Woodfall B, Hoetelmans RMW. 2008. A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers. Br J Clin Pharmacol. 66(4):508–516. doi: 10.1111/j.1365-2125.2008.03214.x.
  • Segregur D, Mann J, Moir A, Karlsson EM, Dressman J. 2021. Prediction of plasma profiles of a weakly basic drug after administration of omeprazole using PBPK modeling. Eur J Pharm Sci. 158:105656. doi: 10.1016/j.ejps.2020.105656.
  • Seibert KD. 2019. Milling operations in the pharmaceutical industry. Chemical Engineering in the Pharmaceutical Industry. p. 861–879.
  • Sharma S, Pepin X, Burri H, Zheng L, Kuptsova-Clarkson N, de Jong A, Yu T, MacArthur HL, Majewski M, Ware JA, et al. 2021. New acalabrutinib formulation enables co-administration with proton pump inhibitors and dosing in patients unable to swallow capsules (ELEVATE-PLUS). Blood. 138(Supplement 1):4365–4365. doi: 10.1182/blood-2021-146610.
  • Shimatani T, Inoue M, Kuroiwa T, Horikawa Y, Mieno H, Nakamura M. 2003. Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2-receptor antagonist. Aliment Pharmacol Ther. 18(11–12):1149–1157. doi: 10.1046/j.1365-2036.2003.01804.x.
  • Shugg T, Powell NR, Marroum PJ, Skaar TC, Younis IR. 2022. Evaluation of US food and drug administration drug label recommendations for coadministration of antivirals and acid-reducing agents. Clin Pharmacol Ther. 112(5):1088–1097. doi: 10.1002/cpt.2723.
  • Siegel IA, Gordon HP. 1986. Surfactant-induced alterations of permeability of rabbit oral mucosa in vitro. Exp Mol Pathol. 44(2):132–137. doi: 10.1016/0014-4800(86)90063-8.
  • Singh A, Van den Mooter G. 2016. Spray drying formulation of amorphous solid dispersions. Adv Drug Deliv Rev. 100:27–50. doi: 10.1016/j.addr.2015.12.010.
  • Smelick GS, Heffron TP, Chu L, Dean B, West DA, Duvall SL, Lum BL, Budha N, Holden SN, Benet LZ, et al. 2013. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development. Mol Pharm. 10(11):4055–4062. doi: 10.1021/mp400403s.
  • Sun W, Klamerus KJ, Yuhas LM, Pawlak S, Plotka A, O’Gorman M, Kirkovsky L, Kosa M, Wang D. 2017. Impact of acid-reducing agents on the pharmacokinetics of palbociclib, a weak base with pH-dependent solubility, with different food intake conditions. Clin Pharmacol Drug Dev. 6(6):614–626. doi: 10.1002/cpdd.356.
  • Sutton SC, Nause R, Gandelman K. 2017. The impact of gastric pH, volume, and emptying on the food effect of ziprasidone oral absorption. AAPS J. 19(4):1084–1090. doi: 10.1208/s12248-017-0065-9.
  • Tartaglia N, Pavone G, Germano MP, Russo G, Pacilli M, Ambrosi A. 2022. Relationship between residual gastric area and weight loss after sleeve gastrectomy: a cohort study. Ann Med Surg (Lond). 73:103177. doi: 10.1016/j.amsu.2021.103177.
  • Tian Y, Fu N, Wu WD, Zhu D, Huang J, Yun S, Chen XD. 2014. Effects of co-spray drying of surfactants with high solids milk on milk powder wettability. Food Bioprocess Technol. 7(11):3121–3135. doi: 10.1007/s11947-014-1323-9.
  • Tolbert MK, Graham A, Odunayo A, Price J, Steiner JM, Newkirk K, Hecht S. 2017. Repeated famotidine administration results in a diminished effect on intragastric pH in dogs. J Vet Intern Med. 31(1):117–123. doi: 10.1111/jvim.14615.
  • Tolman KG, Sanders SW, Buchi KN, Karol MD, Jennings DE, Ringham GL. 1997. The effects of oral doses of lansoprazole and omeprazole on gastric pH. J Clin Gastroenterol. 24(2):65–70. doi: 10.1097/00004836-199703000-00003.
  • US Food and Drug Administration. 2023. Evaluation of gastric pH-dependent drug interactions with acid-reducing agents: study design, data analysis, and clinical implications: guidance for industry.
  • Van Den Abeele J, Kostantini C, Barker R, Kourentas A, Mann JC, Vertzoni M, Beato S, Reppas C, Tack J, Augustijns P, et al. 2020. The effect of reduced gastric acid secretion on the gastrointestinal disposition of a ritonavir amorphous solid dispersion in fasted healthy volunteers: an in vivo – in vitro investigation. Eur J Pharm Sci. 151:105377. doi: 10.1016/j.ejps.2020.105377.
  • Van den Mooter G. 2012. The use of amorphous solid dispersions: a formulation strategy to overcome poor solubility and dissolution rate. Drug Discovery Today: Technologies. 9(2):e79–e85. doi: 10.1016/j.ddtec.2011.10.002.
  • Vimalson DC. 2016. Techniques to enhance solubility of hydrophobic drugs: an overview. Asian Journal of Pharmaceutics (AJP). 10(2).
  • Waller DG, Sampson AP. 2018. 33 – Dyspepsia and peptic ulcer disease. Medical Pharmacology and Therapeutics. 5th ed. Elsevier; p. 401–410.
  • Walravens J, Brouwers J, Spriet I, Tack J, Annaert P, Augustijns P. 2011. Effect of pH and comedication on gastrointestinal absorption of posaconazole. Clin Pharmacokinet. 50(11):725–734. doi: 10.2165/11592630-000000000-00000.
  • Walt RP, Gomes MD, Wood EC, Logan LH, Pounder RE. 1983. Effect of daily oral omeprazole on 24 hour intragastric acidity. Br Med J (Clin Res Ed). 287(6384):12–14. doi: 10.1136/bmj.287.6384.12.
  • Ware JA, Dalziel G, Jin JY, Pellett JD, Smelick GS, West DA, Salphati L, Ding X, Sutton R, Fridyland J, et al. 2013. Impact of food and the proton pump inhibitor rabeprazole on the pharmacokinetics of GDC-0941 in healthy volunteers: bench to bedside investigation of pH-dependent solubility. Mol Pharm. 10(11):4074–4081. doi: 10.1021/mp4005595.
  • Welage LS, Carver PL, Revankar S, Pierson C, Kauffman CA. 1995. Alterations in gastric acidity in patients infected with human immunodeficiency virus. Clin Infect Dis. 21(6):1431–1438. doi: 10.1093/clinids/21.6.1431.
  • Winnick S, Lucas DO, Hartman AL, Toll D. 2005. How do you improve compliance? Pediatrics. 115(6):e718–e724. doi: 10.1542/peds.2004-1133.
  • Wu D, Li M. 2023. Current state and challenges of physiologically based biopharmaceutics modeling (PBBM) in oral drug product development. Pharm Res. 40(2):321–336. doi: 10.1007/s11095-022-03373-0.
  • Wuelfing WP, El Marrouni A, Lipert MP, Daublain P, Kesisoglou F, Converso A, Templeton AC. 2022. Dose number as a tool to guide lead optimization for orally bioavailable compounds in drug discovery. J Med Chem. 65(3):1685–1694. doi: 10.1021/acs.jmedchem.1c01687.
  • Yin OQP, Gallagher N, Fischer D, Demirhan E, Zhou W, Golor G, Schran H. 2010. Effect of the proton pump inhibitor esomeprazole on the oral absorption and pharmacokinetics of Nilotinib. J Clin Pharmacol. 50(8):960–967. doi: 10.1177/0091270009346061.
  • Zhang L, Wu F, Lee SC, Zhao H, Zhang L. 2014. pH-dependent drug-drug interactions for weak base drugs: potential implications for new drug development. Clin Pharmacol Ther. 96(2):266–277. doi: 10.1038/clpt.2014.87.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.