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Pharmaceutics
Jul 19, 2024;16 (7):

Investigation of Stabilized Amorphous Solid Dispersions to Improve Oral Olaparib Absorption.

Taehan Yun, Sumin Lee, Seowan Yun, Daeyeong Cho, Kyuho Bang, Kyeongsoo Kim
Author Information
  1. Taehan Yun: Department of Pharmaceutical Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju 52725, Republic of Korea.
  2. Sumin Lee: Department of Pharmaceutical Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju 52725, Republic of Korea.
  3. Seowan Yun: Department of Pharmaceutical Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju 52725, Republic of Korea.
  4. Daeyeong Cho: Department of Pharmaceutical Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju 52725, Republic of Korea.
  5. Kyuho Bang: Department of Pharmaceutical Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju 52725, Republic of Korea.
  6. Kyeongsoo Kim: Department of Pharmaceutical Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju 52725, Republic of Korea. ORCID
PMID: 39065655 DOI: 10.3390/pharmaceutics16070958

Abstract

In this study, we investigated the formulation of stable solid dispersions to enhance the bioavailability of olaparib (OLA), a therapeutic agent for ovarian cancer and breast cancer characterized as a BCS class IV drug with low solubility and low permeability. Various polymers were screened based on solubility tests, and OLA-loaded solid dispersions were prepared using spray drying. The physicochemical properties of these dispersions were investigated via scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier Transform Infrared Spectroscopy (FT-IR). Subsequent dissolution tests, along with assessments of morphological and crystallinity changes in aqueous solutions, led to the selection of a hypromellose (HPMC)-based OLA solid dispersion as the optimal formulation. HPMC was effective at maintaining the supersaturation of OLA in aqueous solutions and exhibited a stable amorphous state without recrystallization. In an in vivo study, this HPMC-based OLA solid dispersion significantly enhanced bioavailability, increasing AUC by 4.19-fold and C by more than 10.68-fold compared to OLA drug powder (crystalline OLA). Our results highlight the effectiveness of HPMC-based solid dispersions in enhancing the oral bioavailability of OLA and suggest that they could be an effective tool for the development of oral drug formulations.

Keywords

HPMC bioavailability olaparib solid dispersion solubility

References

  1. Mol Pharm. 2013 Sep 3;10(9):3392-403 [PMID: 23829687]
  2. Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):799-813 [PMID: 24056053]
  3. Polymers (Basel). 2022 Nov 09;14(22): [PMID: 36432955]
  4. Drug Dev Ind Pharm. 2015;41(9):1479-87 [PMID: 25224341]
  5. Mol Pharm. 2023 Aug 7;20(8):4153-4164 [PMID: 37433746]
  6. Molecules. 2018 May 11;23(5): [PMID: 29751694]
  7. Int J Pharm. 2010 Jan 4;383(1-2):147-53 [PMID: 19781608]
  8. Drug Dev Ind Pharm. 2014 Aug;40(8):1072-83 [PMID: 23802148]
  9. J Pharm Pharmacol. 2011 Jan;63(1):19-25 [PMID: 21155811]
  10. Pharmaceuticals (Basel). 2021 Apr 22;14(5): [PMID: 33922089]
  11. Pharm Res. 2010 Dec;27(12):2704-14 [PMID: 20859662]
  12. Polim Med. 2013 Oct-Dec;43(4):231-3 [PMID: 24596038]
  13. AAPS PharmSciTech. 2016 Feb;17(1):106-19 [PMID: 26335416]
  14. Eur J Pharm Biopharm. 2017 Apr;113:157-167 [PMID: 28088635]
  15. Acta Pharm Sin B. 2014 Feb;4(1):18-25 [PMID: 26579360]
  16. Drug Discov Ther. 2024 Jan 12;17(6):428-433 [PMID: 38044120]
  17. J Control Release. 2023 Jan;353:42-50 [PMID: 36414193]
  18. Pharmaceutics. 2023 Jun 07;15(6): [PMID: 37376117]
  19. Mol Pharm. 2020 Jan 6;17(1):219-228 [PMID: 31809062]
  20. Int J Mol Sci. 2022 Aug 22;23(16): [PMID: 36012748]
  21. J Basic Clin Physiol Pharmacol. 2019 Dec 14;30(6): [PMID: 31837256]
  22. AAPS PharmSciTech. 2010 Jun;11(2):518-27 [PMID: 20238187]
  23. Carbohydr Polym. 2016 Feb 10;137:350-359 [PMID: 26686139]
  24. Int J Pharm. 2012 May 30;428(1-2):103-13 [PMID: 22414388]
  25. Int J Pharm. 2013 Dec 31;458(2):245-53 [PMID: 24157343]
  26. Int J Pharm. 2020 Aug 30;586:119560 [PMID: 32565285]
  27. Pharmaceutics. 2024 Mar 26;16(4): [PMID: 38675118]
  28. Int J Pharm. 2016 Sep 10;511(1):351-358 [PMID: 27397868]
  29. Eur J Pharm Sci. 2009 Jun 28;37(3-4):241-8 [PMID: 19491011]
  30. AAPS PharmSciTech. 2019 Aug 6;20(7):276 [PMID: 31388783]
  31. Chem Pharm Bull (Tokyo). 2014;62(6):545-51 [PMID: 24881660]
  32. Eur J Med Chem. 2023 Apr 5;252:115300 [PMID: 36989813]
  33. Int J Pharm. 2018 Jan 15;535(1-2):47-58 [PMID: 29097142]
  34. Pharmaceutics. 2020 Feb 25;12(3): [PMID: 32106495]
  35. AAPS J. 2017 May;19(3):806-813 [PMID: 28204967]
  36. Pharm Res. 2018 Apr 23;35(6):125 [PMID: 29687226]
  37. Pharmaceutics. 2019 Mar 19;11(3): [PMID: 30893899]
  38. Antioxidants (Basel). 2023 Mar 08;12(3): [PMID: 36978917]
  39. Eur J Pharm Biopharm. 2019 Feb;135:1-12 [PMID: 30529295]
  40. Pharmaceutics. 2021 Jan 23;13(2): [PMID: 33498609]
  41. Biochim Biophys Acta Rev Cancer. 2020 Jan;1873(1):188319 [PMID: 31678141]
  42. Asian J Pharm Sci. 2019 May;14(3):248-264 [PMID: 32104456]
  43. Int J Pharm. 2002 Dec 5;249(1-2):45-58 [PMID: 12433433]
  44. Pharm Dev Technol. 2017 Feb;22(1):2-12 [PMID: 26616399]
  45. Int J Pharm. 2023 Nov 25;647:123497 [PMID: 37827390]
  46. Sci Rep. 2021 Oct 28;11(1):21255 [PMID: 34711866]
  47. Expert Opin Drug Discov. 2023 Jun;18(6):615-627 [PMID: 37157841]
  48. J Pharm Sci. 2024 Mar;113(3):680-687 [PMID: 37659719]
  49. Int J Pharm. 2005 Jan 31;289(1-2):87-95 [PMID: 15652202]
  50. Int J Prev Med. 2010 Spring;1(2):115-23 [PMID: 21566772]
  51. Int J Pharm. 2010 Jan 4;383(1-2):161-9 [PMID: 19748557]
  52. Mol Pharm. 2023 Aug 7;20(8):4050-4057 [PMID: 37413788]
  53. Front Pharmacol. 2023 Jan 09;13:1054616 [PMID: 36699082]
  54. Eur J Pharm Sci. 2019 Mar 15;130:147-155 [PMID: 30699368]
  55. Mol Pharm. 2012 Jul 2;9(7):2009-16 [PMID: 22632106]
  56. Asian J Pharm Sci. 2019 Nov;14(6):668-676 [PMID: 32104493]
  57. AAPS PharmSciTech. 2015 Apr;16(2):444-54 [PMID: 25361900]
  58. Pharmaceutics. 2019 Sep 25;11(10): [PMID: 31557831]
  59. AAPS PharmSciTech. 2020 Nov 8;21(8):309 [PMID: 33161493]
  60. Int J Mol Sci. 2024 Jan 18;25(2): [PMID: 38256270]
  61. Target Oncol. 2018 Dec;13(6):801-808 [PMID: 30456461]
  62. Drug Des Devel Ther. 2020 Jul 27;14:2959-2975 [PMID: 32801637]
  63. Ther Drug Monit. 2023 Jun 1;45(3):306-317 [PMID: 36728223]
  64. Carbohydr Polym. 2021 Nov 1;271:118433 [PMID: 34364573]
  65. Pharm Res. 2008 Mar;25(3):647-56 [PMID: 17846870]
  66. Sci Rep. 2020 Oct 28;10(1):18535 [PMID: 33116200]
  67. Drug Dev Ind Pharm. 2019 Aug;45(8):1277-1291 [PMID: 31111732]
  68. Adv Colloid Interface Sci. 2015 Sep;223:40-54 [PMID: 26043877]
  69. Int J Pharm. 2001 May 7;218(1-2):27-42 [PMID: 11337147]
Journal Article

Word Cloud

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