Approaches to Improve Oral Bioavailability of Antihypertensive Drugs: A Mini-Review


Hypertension elevates the risk of heart disease and stroke which are one of the most frequent causes of death. Fortunately, hypertension is manageable with the use of anti-hypertensives and a healthy lifestyle. However, patient non-adherence to the prescribed dosing regimen is the primary reason for uncontrolled blood pressure levels. Daily multiple doses of medication are one of the major reasons for patient non-compliance to the dosing regimen. Multiple doses of medication are a result of low solubility and high first-pass metabolism of anti-hypertensives. There are several approaches to improve the bioavailability of anti-hypertensives like polymeric and non-polymeric approaches to enhance solubility, avoiding first-pass metabolism through alternate routes of drug delivery and others. The objective of this review is to discuss different approaches to enhance the oral bioavailability of anti-hypertensive drugs.

Keywords: Solubility enhancements, solid lipid nanoparticles, hot melt extrusion, drug delivery, pharmacokinetics, poorly soluble, oral bioavailability.

Keywords: Solubility enhancements, solid lipid nanoparticles, hot melt extrusion, drug delivery, pharmacokinetics, poorly soluble, oral bioavailability


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Author Biographies

Radhika Dole, Vaagdevi Pharmacy College, Bollikunta, Warangal, Telangana, 506005

Vaagdevi Pharmacy College, Bollikunta, Warangal, Telangana, 506005

Daniel Kothapally, Chaitanya Deemed to be University, Hanamkonda, Warangal, Telangana, 506001

Chaitanya Deemed to be University, Hanamkonda, Warangal, Telangana, 506001

Sampoorna Chukkala, Talla Padmavathi Pharmacy College, Orus, Kareemabad, Warangal, Telangana, 506002

Talla Padmavathi Pharmacy College, Orus, Kareemabad, Warangal, Telangana, 506002

Ravi Chander Thatipelli, Vaagdevi Pharmacy College, Bollikunta, Warangal, Telangana, 506005

Vaagdevi Pharmacy College, Bollikunta, Warangal, Telangana, 506005


1. [last accessed 07 March 2023].
2. [last accessed 07 March 2023]
3. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nature Reviews Nephrology. 2020 Apr; 16(4):223-37.
4. [last accessed 07 March 2023]
5. Devi P, Rao M, Sigamani A, Faruqui A, Jose M, Gupta R, Kerkar P, Jain RK, Joshi R, Chidambaram N, Rao DS. Prevalence, risk factors and awareness of hypertension in India: a systematic review. Journal of human hypertension. 2013 May; 27(5):281-7.
6. Gupta R. Trends in hypertension epidemiology in India. Journal of human hypertension. 2004 Feb; 18(2):73-8.
7. Prabhakaran D, Jeemon P, Roy A. Cardiovascular diseases in India: current epidemiology and future directions. Circulation. 2016 Apr 19; 133(16):1605-20.
8. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2018 May 15; 71(19):e127-248.
9. Houston MC, Bell L. Controlling High Blood Pressure Through Nutrition, Supplements, Lifestyle and Drugs, CRC Press, 2021.
10. Samanthula KS, Kumar CB M, Bairi AG, Satla SR. Development, in-vitro and ex-vivo evaluation of muco-adhesive buccal tablets of hydralazine hydrochloride. Brazilian Journal of Pharmaceutical Sciences. 2022 Apr 22; 58.
11. Baishya BI, Rahman SS, Rynjah DA, Barman KA, Bordoloi SS, Islam JA, Hasan N. Enhancing of oral bioavailability of poorly water-soluble antihypertensive drugs. Int J Curr Pharm Res. 2021; 13(4):42-7.
12. Prisant LM, Bottini B, DiPiro JT, Carr AA. Novel drug-delivery systems for hypertension. Am J Med. 1992 Aug 31; 93(2A):45S-55S.
13. Samanthula KS, Bairi AG, Kumar M. Development, in-vitro and in-vivo Evaluation of Bio-Adhesive Buccal Patches of Hydralazine Hydrochloride for Improving the Oral Bioavailability. International Journal of Pharmacy and Biological Sciences, 2021; 11(2):138-148.
14. Alam T, Khan S, Gaba B, Haider MF, Baboota S, Ali J. Nanocarriers as treatment modalities for hypertension. Drug delivery. 2017 Jan 1; 24(1):358-69.
15. Muddineti OS, Kumari P, Ajjarapu S, Lakhani PM, Bahl R, Ghosh B, Biswas S. Xanthan gum stabilized PEGylated gold nanoparticles for improved delivery of curcumin in cancer. Nanotechnology. 2016 Jun 27; 27(32):325101.
16. Chaudhari S, Nikam SA, Khatri N, Wakde S, Co-crystals: a review, Journal of Drug Delivery and Therapeutics. 2018; 8(6-s):350-358
17. Ajjarapu S, Banda S, Basim P, Dudhipala N. Melt Fusion Techniques for Solubility Enhancement: A Comparison of Hot Melt Extrusion and KinetiSol® Technologies. Scientia Pharmaceutica. 2022 Aug 24; 90(3):51.
18. Perrut M, Jung J, Leboeuf F. Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes: Part I: Micronization of neat particles. International journal of pharmaceutics. 2005 Jan 6; 288(1):3-10.
19. Butreddy A, Sarabu S, Almutairi M, Ajjarapu S, Kolimi P, Bandari S, Repka MA. Hot-melt extruded hydroxypropyl methylcellulose acetate succinate based amorphous solid dispersions: Impact of polymeric combinations on supersaturation kinetics and dissolution performance. International Journal of Pharmaceutics. 2022 Mar 5; 615:121471.
20. Ajjarapu S, Rangappa S, Shankar VK, Shettar A, Kumar HS, Kulkarni VI, Repka MA, Murthy SN. A rapid tool to optimize process variables for continuous manufacturing of metronidazole ointment using melt extrusion technique. AAPS PharmSciTech. 2020 Oct; 21:1-7.
21. Giri BR, Kwon J, Vo AQ, Bhagurkar AM, Bandari S, Kim DW. Hot-melt extruded amorphous solid dispersion for solubility, stability, and bioavailability enhancement of telmisartan. Pharmaceuticals. 2021 Jan 18; 14(1):73.
22. Jadhav P, Gokarna V, Deshpande V, Vavia P. bioavailability enhancement of olmesartan medoxomil using hot-melt extrusion: In-silico, in-vitro, and in-vivo evaluation. AAPS PharmSciTech. 2020 Oct; 21:1-7.
23. Fu Q, Fang M, Hou Y, Yang W, Shao J, Guo M, Li M, Li J, Wang Y, He Z, Sun J. A physically stabilized amorphous solid dispersion of nisoldipine obtained by hot melt extrusion. Powder Technology. 2016 Nov 1; 301:342-8.
24. Jaipal A, Pandey MM, Charde SY, Sadhu N, Srinivas A, Prasad RG. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies. Drug delivery. 2016 Feb 12; 23(2):452-8.
25. Khafagy ES, Abu Lila AS, Sallam NM, Sanad RA, Ahmed MM, Ghorab MM, Alotaibi HF, Alalaiwe A, Aldawsari MF, Alshahrani SM, Alshetaili A. Preparation and Characterization of a Novel Mucoadhesive Carvedilol Nanosponge: A Promising Platform for Buccal Anti-Hypertensive Delivery. Gels. 2022 Apr 11; 8(4):235.
26. Bansal S, Bansal M, Garg G. Preparation and evaluation of buccoadhesive patches of an antihypertensive drug. Am. J. Phytomed. Clin. Ther. 2013; 1(2):240-55.
27. Samanthula KS, Satla SR, Bairi AG. Development, In-Vitro and Ex-Vivo Evaluation of Muco-adhesive Buccal patches of Candesartan cilexetil. Research Journal of Pharmacy and Technology. 2019; 12(6):3038-44.
28. Maurya A, Rangappa S, Bae J, Dhawan T, Ajjarapu SS, Murthy SN. Evaluation of soluble fentanyl microneedles for loco-regional anti-nociceptive activity. International journal of pharmaceutics. 2019 Jun 10; 564:485-91.
29. Dhadwal A, Sharma DR, Pandit V, Ashawat MS, Kumar P, Cubosomes: A novel carrier for transdermal drug delivery, Journal of drug delivery and therapeutics. 2010; 10(1):123-130.
30. Shettar A, Shankar VK, Ajjarapu S, Kulkarni VI, Repka MA, Murthy SN. Development and characterization of Novel topical oil/PEG creams of voriconazole for the treatment of fungal infections. Journal of Drug Delivery Science and Technology. 2021 Dec 1; 66:102928.
31. Aqil M, Ali A, Sultana Y, Dubey K, Najmi AK, Pillai KK. In vivo characterization of monolithic matrix type transdermal drug delivery systems of pinacidil monohydrate: A technical note. AAPS PharmSciTech. 2006 Mar; 7:E38-42.
32. Baviskar DT, Parik VB, Gupta HN, Maniyar AH, Jain DK. Design and evaluation of patches for transdermal delivery of losartan potassium. PDA Journal of Pharmaceutical Science and Technology. 2012 Mar 1; 66(2):126-35.
33. Morsi NM, Aboelwafa AA, Dawoud MH. Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study. Journal of Liposome Research. 2018 Apr 3; 28(2):137-48.
34. Pridgen EM, Alexis F, Farokhzad OC. Polymeric nanoparticle technologies for oral drug delivery. Clinical Gastroenterology and Hepatology. 2014 Oct 1; 12(10):1605-10.
35. Dudhipala N. A comprehensive review on solid lipid nanoparticles as delivery vehicle for enhanced pharmacokinetic and pharmacodynamic activity of poorly soluble drugs. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN). 2019 Mar 31; 12(2):4421-40.
36. Dudhipala N. Influence of solid lipid nanoparticles on pharmaco-dynamic activity of poorly oral bioavailable drugs. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN). 2020 Jul 11; 13(4):4979-83.
37. Thirupathi G, Swamy SK, Ramesh A. Solid lipid nanocarriers as alternative drug delivery system for improved oral delivery of drugs. Journal of Drug Delivery and Therapeutics. 2020 Dec 15; 10(6-s):168-72.
38. Kishan V, Sandeep V, Narendar D, Arjun N. Lacidipine loaded solid lipid nanoparticles for oral delivery: preparation, characterization and in vivo evaluation. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN). 2016 Nov 30; 9(6):3524-30.
39. Samanthula KS, Alli R, Gorre T. Preparation, In Vitro characterization and stability studies of ropinirole lipid nanoparticles enriched hydrogel for treatment of neurodegeneration diseases. Journal of Drug Delivery and Therapeutics. 2021 Apr 15; 11(2-S):66-75.
40. Mallesh K, Pasula N, Kumar Ranjith CP. Piroxicam proliposomal gel: a novel approach for tropical delivery. Journal of Pharmacy Research. 2012; 5(3):1755-63.
41. Basim P, Gorityala S, Kurakula M. Advances in functionalized hybrid biopolymer augmented lipid-based systems: A spotlight on their role in design of gastro retentive delivery systems. Archives of Gastroenterology Research. 2021 Mar 2; 2(1):35-47.
42. Shah HG, Rathod V, Basim P, Gajera B, Dave RH. Understanding the Impact of Multi-factorial Composition on Efficient Loading of the Stable Ketoprofen Nanoparticles on Orodispersible Films Using Box-Behnken Design. Journal of Pharmaceutical Sciences. 2022 May 1; 111(5):1451-62.
43. Dudhipala N, Veerabrahma K. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug delivery. 2016 Feb 12; 23(2):395-404.
44. Kurakula M, Patel DB, Patel B, Gorityala S, Basim P. Functionalized Nanocarriers for Drug delivery: Amalgam of Biopolymers and Lipids. J Nanomed. 2021; 4(1):1037.
45. Samanthula KS, Bairi AG, Kumar CM. Muco-adhesive buccal tablets of candesartan cilexetil for oral delivery: preparation, in-vitro and ex-vivo evaluation. Journal of Drug Delivery and Therapeutics. 2021 Feb 15; 11(1-s):35-42.
46. Butreddy A, Janga KY, Ajjarapu S, Sarabu S, Dudhipala N. Instability of therapeutic proteins-An overview of stresses, stabilization mechanisms and analytical techniques involved in Lyophilized proteins. International journal of biological macromolecules. 2021 Jan 15; 167:309-25.
47. Narendar D, Kishan V. Candesartan cilexetil nanoparticles for improved oral bioavailability. Ther deli. 2017; 8(2):79-88.
48. Thirupathi G, Swetha E, Narendar D. Role of isradipine loaded solid lipid nanoparticles on the pharmacodynamic effect in rats. Drug research. 2017 Mar; 67(03):163-9.
49. Kishan V, Suram D, Yeleshwarapu S, Dudhipala N. Development, Characterization and Comparative Phar-macokinetic Evaluation of Ritonavir Nanosuspension, with a Model Nanoemulsion and Coarse Suspension for Improved Oral Delivery. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN). 2021 May 6; 14(3):5462-71.
50. Siekmann B, Westesen K. Submicron-sized parenteral carrier systems based on solid lipids. Pharm. Pharmacol. Lett. 1992; 1(3):123-6.
51. Nagaraj B, Tirumalesh C, Dinesh S, Narendar D. Zotepine loaded lipid nanoparticles for oral delivery: development, characterization, and in vivo pharmacokinetic studies. Future Journal of Pharmaceutical Sciences. 2020 Dec; 6:1-1.
52. Mistry SN, Patel PK, Bharadia PD, Pandya VM, Modi DA. Novel drug delivery system for lipophilic agents: solid lipid nanoparticles. J Pharm Cosmetol. 2011;1:76-89.
53. Yang SC, Lu LF, Cai Y, Zhu JB, Liang BW, Yang CZ. Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain. Journal of controlled release. 1999 Jun 2; 59(3):299-307.
54. Wang, Taoran, Qiaobin Hu, Ji-Young Lee, and Yangchao Luo. "Solid lipid-polymer hybrid nanoparticles by in situ conjugation for oral delivery of astaxanthin." Journal of agricultural and food chemistry 2018; 66(36):9473-9480.
55. Dudhipala N, Veerabrahma K. Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug development and industrial pharmacy. 2015 Dec 2; 41(12):1968-77.
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How to Cite
Dole R, Kothapally D, Chukkala S, Thatipelli RC. Approaches to Improve Oral Bioavailability of Antihypertensive Drugs: A Mini-Review. JDDT [Internet]. 15May2023 [cited 18May2024];13(5):73-7. Available from: