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pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension

Yıl 2023, Cilt: 27 Sayı: 2, 848 - 859, 27.06.2025

Dr. Abhishek Kanugo , Ronit Dhage

Öz

The greatest number of mortality in the world occurred due to hypertension. Several bodily
functions are based on circadian rhythm including hypertension. The stimulation of the sympathetic
nervous system in the early morning hours resulted in accelerating blood pressure which is a highly
dangerous condition. This lead to cardiac failure and damage to the vital organs of the body. The current
research focuses on pulsatile delivery of Ambrisentan for the treatment of high blood pressure which
released the medicament at the right time and the right place. Primarily, core tablets were prepared with
Ambrisentan. The compatibility of Ambrisentan with excipients was confirmed by FTIR analysis. The core
tablets were evaluated for flowing characteristics which showed better flowing behavior and optimized
core batch CT6 showed consolidation index 16.07±0.11 and angle of repose 27.02±0.14. Moreover, due to the
least disintegration time (2.23±0.10) and greater dissolution release of 99.70 % ±0.49, CT6 was selected as an
optimized core tablet for pulsatile delivery. Further, the combination of Eudragit L100 and ethyl cellulose
were utilized for coating purposes in different proportion were utilized for achieving the desired lag time
of 6 hrs. The optimized batch PC6 (Eudragit L100: EC 10) which comprised of 25:75 proportion showed a
lag time of 6 hours, cumulative release of 99.25 % and content uniformity of 99.29±0.82. The dissolution
release profile predicted zero-order release for Ambrisentan pulsatile tablets. The accelerated stability
testing showed minimal loss of drug content when exposed at 40 0C and 75 % relative humidity without
altering lag time.

Anahtar Kelimeler

Ambrisentan Pulmonary hypertension Pulsatile delivery Eudragit L100 Ethylcellulose

Kaynakça

  • Kee HJ, Kim I, Jeong MH. Zinc-dependent histone deacetylases: Potential therapeutic targets for arterial hypertension. Biochem Pharmacol. 2022;202:115111. [CrossRef]
  • Tomaszewski M, Morris AP, Howson JM, Franceschini N, Eales J, Xu X, et al. Kidney omics in hypertension – from statistical associations to biological mechanisms and clinical applications. Kidney Int [Internet]. 2022 Jun 9 [cited 2022 Jun 10]; [CrossRef]
  • Al Attar AA, Fahed GI, Hoballah MM, Pedersen S, El-Yazbi AF, Nasser SA, et al. Mechanisms underlying the effects of caloric restriction on hypertension. Biochem Pharmacol. 2022 Jun 1;200:115035. [CrossRef]
  • Wójcik M, Kozioł-Kozakowska A. Obesity, Sodium Homeostasis, and Arterial Hypertension in Children and Adolescents. Nutrients [Internet]. 2021 Nov 1 [cited 2022 Jun 10];13(11). [CrossRef]
  • Tanaka M, Itoh H. Hypertension as a Metabolic Disorder and the Novel Role of the Gut. Curr Hypertens Rep [Internet]. 2019 Aug 1 [cited 2022 Jun 10];21(8):1–10. [CrossRef]
  • Ames MK, Atkins CE, Pitt B. The renin‐angiotensin‐aldosterone system and its suppression. J Vet Intern Med [Internet]. 2019 Mar 1 [cited 2022 Jun 10];33(2):363. [CrossRef]
  • Hajra A, Safiriyu I, Balasubramanian P, Gupta R, Chowdhury S, Prasad AJ, et al. Recent Advances and Future Prospects of Treatment of Pulmonary Hypertension. Curr Probl Cardiol. 2022 Apr 29;101236. [CrossRef]
  • Morris M, Yamazaki S, Stefanovska A. Multiscale Time-resolved Analysis Reveals Remaining Behavioral Rhythms in Mice Without Canonical Circadian Clocks. J Biol Rhythms [Internet]. 2022 Jun [cited 2022 Jun 10];37(3):310–28. [CrossRef]
  • Douma LG, Gumz ML. Circadian Clock-Mediated Regulation of Blood Pressure. Free Radic Biol Med [Internet]. 2018 May 5 [cited 2022 Jun 10];119:108. [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar AV. Development of pulsatile drug delivery for chronotherapeutics of hypertension. Int J Drug Deliv Technol. 2017;7(3). [CrossRef]
  • Sreejan M, Krishnaveni V, Sai Padmini, Satyavathi K, Bhojaraju P, Madhubabu M. Design and Evaluation of Chronotherapeutic Delivery of Terbutaline Sulphate by Pulsincap Technology. Int J Drug Deliv Technol. 2017;7(1):75–82. [CrossRef]
  • Dabhi C, Randale S, Belgamwar V, Gattani S, Tekade A. Predictable pulsatile release of tramadol hydrochloride for chronotherapeutics of arthritis. 2010;17(5):273–81. [CrossRef]
  • Penhasi A, Gomberg M. Design and development of an innovative water insoluble fi lm-coating combination for oral pulsatile drug delivery. J Drug Deliv Sci Technol [Internet]. 2018;43(October 2017):274–82. [CrossRef]
  • Zhang Z, Qi X, Li X, Xing J, Zhu X, Wu Z. A novel pulsatile drug delivery system based on the physiochemical reaction between acrylic copolymer and organic acid: In vitro and in vivo evaluation. Int J Pharm [Internet]. 2014;462(1–2):66–73. [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar AV. pH dependent pulsatile drug delivery for chronotherapeutics of cardiovascular diseases. Der Pharma Lettre 2017; 260–9.
  • Vani C, Reddy KS. Pulsatile drug delivery system-a technique of delivering drug in accordance with biological clock-a review. Int J Adv Res [Internet]. [cited 2022 Jun 6];9(05):101–24. [CrossRef]
  • Ambrisentan: Uses, Interactions, Mechanism of Action | DrugBank Online [Internet]. [cited 2021 Sep 19]. Available from: https://go.drugbank.com/drugs/DB06403. [CrossRef]
  • Kanugo A. Liquisolid-pellets technique: A recent technique for enhancing solubility and bioavailability of drugs. Int J Appl Pharm. 2020;12(6):34–40. [CrossRef
  • Parmar K, Shaikh A, Dalvadi H. Chronomodulated drug delivery system of Irbesartan: Formulation and development using Desing of Experiment (DoE). Bull Fac Pharmacy, Cairo Univ [Internet]. 2018;56(1):11–7. [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar AV, Dhabarde DM, Dhawral VG. Design and evaluation of enteric compression-coated tablet for chronotherapeutic drug delivery. Asian J Pharm. 2017;11(3). [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar A. Pulsatile drug delivery of candesartan cilexetil for cardiovascular complications. Int J Pharm Sci Res 2017;8(9):3928–35.. [CrossRef]
  • Roy SK, Das P, Mondal A, Mandal A, Kuotsu K. Design , formulation and evaluation of multiparticulate time programmed system of ramipril for pulsed release : An approach in the management of early morning surge in blood pressure. J Drug Deliv Sci Technol [Internet]. 2021;62(November 2020):102344. [CrossRef]
  • Kanugo AY, Mathur VB. Evaluation and Comparison of Highly Soluble Sodium Stearyl Fumarate with Other Lubricants In Vitro. Indo Am J Pharm Res 2013;3:4042-4049.
  • Rashid R, Zaman M, Ahmad M, Khan MA, Butt MH, Salawi A, et al. Press-Coated Aceclofenac Tablets for Pulsatile Drug Delivery: Formulation and In Vitro Evaluations. Pharmaceuticals. 2022;15(3):1–19. [CrossRef]
  • Hellberg E, Westberg A, Appelblad P, Mattsson S. Evaluation of dissolution techniques for orally disintegrating mini-tablets. J Drug Deliv Sci Technol. 2021 Feb 1;61:102191. [CrossRef]
  • Li R, Pan Y, Chen D, Xu X, Yan G, Fan T. Design, Preparation and In Vitro Evaluation of Core–Shell Fused Deposition Modelling 3D-Printed Verapamil Hydrochloride Pulsatile Tablets. Pharmaceutics. 2022;14(2). [CrossRef]
  • Kokott M, Lura A, Breitkreutz J, Wiedey R. Evaluation of two novel co-processed excipients for direct compression of orodispersible tablets and mini-tablets. Eur J Pharm Biopharm [Internet]. 2021 Nov 1 [cited 2021 Sep 19];168:122–30. [CrossRef]
  • Gowthami B, Krishna SVG, Rao DS. Formulation of Tablets in Capsule system : Statistical optimization for chronotherapeutic drug delivery of propranolol hydrochloride. 2021;63(October 2020). [CrossRef]
  • Biswas N, Kuotsu K. Chronotherapeutically Modulated Pulsatile System of Valsartan Nanocrystals—an In Vitro and In Vivo Evaluation. AAPS PharmSciTech. 2017;18(2):349–57. [CrossRef]
  • Bello ML, Junior AM, Freitas CA, Moreira MLA, Juliana P, Souza MA De, et al. European Journal of Pharmaceutical Sciences Development of novel montmorillonite-based sustained release system for oral bromopride delivery . 2022;175(May). [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar A . Predictable Pulsatile Release of Candesartan Cilexetil for Chronotherapeutics of Hypertension. Int J Drug Dev Res. 2017;9(2):42–7
  • Patadia R, Vora C, Mittal K, Mashru RC. Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology. AAPS PharmSciTech [Internet]. 2017;18(4):1213–27. [CrossRef]
  • Dahmash EZ, Iyire A, Alyami HS. Development of orally dissolving films for pediatric-centric administration of anti-epileptic drug topiramate – A design of experiments (DoE) study. Saudi Pharm J. 2021 Jul 1;29(7):635–47. [CrossRef]
  • Kallakunta VR, Sarabu S, Dudhipala N, Janga KY, Bandari S, Zhang F, et al. Chrono modulated multiple unit particulate systems (MUPS) via a continuous hot melt double extrusion technique: Investigation of the formulation and process suitability. Eur J Pharm Biopharm [Internet]. 2021;168(May):184–94. [CrossRef]

Yıl 2023, Cilt: 27 Sayı: 2, 848 - 859, 27.06.2025

Dr. Abhishek Kanugo , Ronit Dhage

Öz

Kaynakça

  • Kee HJ, Kim I, Jeong MH. Zinc-dependent histone deacetylases: Potential therapeutic targets for arterial hypertension. Biochem Pharmacol. 2022;202:115111. [CrossRef]
  • Tomaszewski M, Morris AP, Howson JM, Franceschini N, Eales J, Xu X, et al. Kidney omics in hypertension – from statistical associations to biological mechanisms and clinical applications. Kidney Int [Internet]. 2022 Jun 9 [cited 2022 Jun 10]; [CrossRef]
  • Al Attar AA, Fahed GI, Hoballah MM, Pedersen S, El-Yazbi AF, Nasser SA, et al. Mechanisms underlying the effects of caloric restriction on hypertension. Biochem Pharmacol. 2022 Jun 1;200:115035. [CrossRef]
  • Wójcik M, Kozioł-Kozakowska A. Obesity, Sodium Homeostasis, and Arterial Hypertension in Children and Adolescents. Nutrients [Internet]. 2021 Nov 1 [cited 2022 Jun 10];13(11). [CrossRef]
  • Tanaka M, Itoh H. Hypertension as a Metabolic Disorder and the Novel Role of the Gut. Curr Hypertens Rep [Internet]. 2019 Aug 1 [cited 2022 Jun 10];21(8):1–10. [CrossRef]
  • Ames MK, Atkins CE, Pitt B. The renin‐angiotensin‐aldosterone system and its suppression. J Vet Intern Med [Internet]. 2019 Mar 1 [cited 2022 Jun 10];33(2):363. [CrossRef]
  • Hajra A, Safiriyu I, Balasubramanian P, Gupta R, Chowdhury S, Prasad AJ, et al. Recent Advances and Future Prospects of Treatment of Pulmonary Hypertension. Curr Probl Cardiol. 2022 Apr 29;101236. [CrossRef]
  • Morris M, Yamazaki S, Stefanovska A. Multiscale Time-resolved Analysis Reveals Remaining Behavioral Rhythms in Mice Without Canonical Circadian Clocks. J Biol Rhythms [Internet]. 2022 Jun [cited 2022 Jun 10];37(3):310–28. [CrossRef]
  • Douma LG, Gumz ML. Circadian Clock-Mediated Regulation of Blood Pressure. Free Radic Biol Med [Internet]. 2018 May 5 [cited 2022 Jun 10];119:108. [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar AV. Development of pulsatile drug delivery for chronotherapeutics of hypertension. Int J Drug Deliv Technol. 2017;7(3). [CrossRef]
  • Sreejan M, Krishnaveni V, Sai Padmini, Satyavathi K, Bhojaraju P, Madhubabu M. Design and Evaluation of Chronotherapeutic Delivery of Terbutaline Sulphate by Pulsincap Technology. Int J Drug Deliv Technol. 2017;7(1):75–82. [CrossRef]
  • Dabhi C, Randale S, Belgamwar V, Gattani S, Tekade A. Predictable pulsatile release of tramadol hydrochloride for chronotherapeutics of arthritis. 2010;17(5):273–81. [CrossRef]
  • Penhasi A, Gomberg M. Design and development of an innovative water insoluble fi lm-coating combination for oral pulsatile drug delivery. J Drug Deliv Sci Technol [Internet]. 2018;43(October 2017):274–82. [CrossRef]
  • Zhang Z, Qi X, Li X, Xing J, Zhu X, Wu Z. A novel pulsatile drug delivery system based on the physiochemical reaction between acrylic copolymer and organic acid: In vitro and in vivo evaluation. Int J Pharm [Internet]. 2014;462(1–2):66–73. [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar AV. pH dependent pulsatile drug delivery for chronotherapeutics of cardiovascular diseases. Der Pharma Lettre 2017; 260–9.
  • Vani C, Reddy KS. Pulsatile drug delivery system-a technique of delivering drug in accordance with biological clock-a review. Int J Adv Res [Internet]. [cited 2022 Jun 6];9(05):101–24. [CrossRef]
  • Ambrisentan: Uses, Interactions, Mechanism of Action | DrugBank Online [Internet]. [cited 2021 Sep 19]. Available from: https://go.drugbank.com/drugs/DB06403. [CrossRef]
  • Kanugo A. Liquisolid-pellets technique: A recent technique for enhancing solubility and bioavailability of drugs. Int J Appl Pharm. 2020;12(6):34–40. [CrossRef
  • Parmar K, Shaikh A, Dalvadi H. Chronomodulated drug delivery system of Irbesartan: Formulation and development using Desing of Experiment (DoE). Bull Fac Pharmacy, Cairo Univ [Internet]. 2018;56(1):11–7. [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar AV, Dhabarde DM, Dhawral VG. Design and evaluation of enteric compression-coated tablet for chronotherapeutic drug delivery. Asian J Pharm. 2017;11(3). [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar A. Pulsatile drug delivery of candesartan cilexetil for cardiovascular complications. Int J Pharm Sci Res 2017;8(9):3928–35.. [CrossRef]
  • Roy SK, Das P, Mondal A, Mandal A, Kuotsu K. Design , formulation and evaluation of multiparticulate time programmed system of ramipril for pulsed release : An approach in the management of early morning surge in blood pressure. J Drug Deliv Sci Technol [Internet]. 2021;62(November 2020):102344. [CrossRef]
  • Kanugo AY, Mathur VB. Evaluation and Comparison of Highly Soluble Sodium Stearyl Fumarate with Other Lubricants In Vitro. Indo Am J Pharm Res 2013;3:4042-4049.
  • Rashid R, Zaman M, Ahmad M, Khan MA, Butt MH, Salawi A, et al. Press-Coated Aceclofenac Tablets for Pulsatile Drug Delivery: Formulation and In Vitro Evaluations. Pharmaceuticals. 2022;15(3):1–19. [CrossRef]
  • Hellberg E, Westberg A, Appelblad P, Mattsson S. Evaluation of dissolution techniques for orally disintegrating mini-tablets. J Drug Deliv Sci Technol. 2021 Feb 1;61:102191. [CrossRef]
  • Li R, Pan Y, Chen D, Xu X, Yan G, Fan T. Design, Preparation and In Vitro Evaluation of Core–Shell Fused Deposition Modelling 3D-Printed Verapamil Hydrochloride Pulsatile Tablets. Pharmaceutics. 2022;14(2). [CrossRef]
  • Kokott M, Lura A, Breitkreutz J, Wiedey R. Evaluation of two novel co-processed excipients for direct compression of orodispersible tablets and mini-tablets. Eur J Pharm Biopharm [Internet]. 2021 Nov 1 [cited 2021 Sep 19];168:122–30. [CrossRef]
  • Gowthami B, Krishna SVG, Rao DS. Formulation of Tablets in Capsule system : Statistical optimization for chronotherapeutic drug delivery of propranolol hydrochloride. 2021;63(October 2020). [CrossRef]
  • Biswas N, Kuotsu K. Chronotherapeutically Modulated Pulsatile System of Valsartan Nanocrystals—an In Vitro and In Vivo Evaluation. AAPS PharmSciTech. 2017;18(2):349–57. [CrossRef]
  • Bello ML, Junior AM, Freitas CA, Moreira MLA, Juliana P, Souza MA De, et al. European Journal of Pharmaceutical Sciences Development of novel montmorillonite-based sustained release system for oral bromopride delivery . 2022;175(May). [CrossRef]
  • Kanugo AY, Kochar NI, Chandewar A . Predictable Pulsatile Release of Candesartan Cilexetil for Chronotherapeutics of Hypertension. Int J Drug Dev Res. 2017;9(2):42–7
  • Patadia R, Vora C, Mittal K, Mashru RC. Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology. AAPS PharmSciTech [Internet]. 2017;18(4):1213–27. [CrossRef]
  • Dahmash EZ, Iyire A, Alyami HS. Development of orally dissolving films for pediatric-centric administration of anti-epileptic drug topiramate – A design of experiments (DoE) study. Saudi Pharm J. 2021 Jul 1;29(7):635–47. [CrossRef]
  • Kallakunta VR, Sarabu S, Dudhipala N, Janga KY, Bandari S, Zhang F, et al. Chrono modulated multiple unit particulate systems (MUPS) via a continuous hot melt double extrusion technique: Investigation of the formulation and process suitability. Eur J Pharm Biopharm [Internet]. 2021;168(May):184–94. [CrossRef]
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Dr. Abhishek Kanugo 0000-0002-5205-5906

Ronit Dhage 0000-0002-8079-7448

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 2

Kaynak Göster

APA Kanugo, D. A., & Dhage, R. (2025). pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension. Journal of Research in Pharmacy, 27(2), 848-859.
AMA Kanugo DA, Dhage R. pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension. J. Res. Pharm. Haziran 2025;27(2):848-859.
Chicago Kanugo, Dr. Abhishek, ve Ronit Dhage. “PH-Dependent Pulsatile Delivery of Ambrisentan for the Treatment of Hypertension”. Journal of Research in Pharmacy 27, sy. 2 (Haziran 2025): 848-59.
EndNote Kanugo DA, Dhage R (01 Haziran 2025) pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension. Journal of Research in Pharmacy 27 2 848–859.
IEEE D. A. Kanugo ve R. Dhage, “pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension”, J. Res. Pharm., c. 27, sy. 2, ss. 848–859, 2025.
ISNAD Kanugo, Dr. Abhishek - Dhage, Ronit. “PH-Dependent Pulsatile Delivery of Ambrisentan for the Treatment of Hypertension”. Journal of Research in Pharmacy 27/2 (Haziran 2025), 848-859.
JAMA Kanugo DA, Dhage R. pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension. J. Res. Pharm. 2025;27:848–859.
MLA Kanugo, Dr. Abhishek ve Ronit Dhage. “PH-Dependent Pulsatile Delivery of Ambrisentan for the Treatment of Hypertension”. Journal of Research in Pharmacy, c. 27, sy. 2, 2025, ss. 848-59.
Vancouver Kanugo DA, Dhage R. pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension. J. Res. Pharm. 2025;27(2):848-59.