Nasal Mucoadhesive Microspheres of Lercanidipine with Improved Systemic Bioavailability and Antihypertensive Activity
Tóm tắt
The current study entails the design, development, and optimization of nasal mucoadhesive microspheres of lercanidipine with improved systemic bioavailability for the management of hypertension. Mucoadhesive microspheres of lercanidipine were prepared by solvent evaporation and polymerization method using bovine serum albumin (BSA) as the carrier and glutaraldehyde as the chelating agent. For screening the material and process variables, Taguchi design revealed the major influence of BSA concentration and glutaraldehyde volume as the critical factors for the preparation of microspheres. These factors were systematically optimized using Central Composite design to evaluate the particle size, entrapment efficiency, and in vitro drug release from the microspheres as the response variables. The optimized microspheres were prepared using 4.4% BSA and 0.25-mL glutaraldehyde, and stirring speed at 1500 rpm, which exhibited particle size of 34 μm, entrapment efficiency of 88.6%, Q6h of 94.67%, T60% of 3.2 h, and bioadhesion efficiency of 93.2%. In vivo pharmacokinetics in rabbits showed remarkable superiority of the optimized nasal microspheres (p < 0.001) with nearly eightfold improvement in the drug absorption parameters vis-à-vis the pure drug lercanidipine. Accelerated stability studies for 6 months demonstrated nearly similar drug release profiles at different time intervals, indicating the robustness of the optimized formulation. In a nutshell, the present studies resulted in the successful development of optimized lercanidipine microspheres for nasal delivery.
Tài liệu tham khảo
Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, et al. Drug delivery systems: an updated review. Int J Pharm Investig. 2013;2(1):2–11.
Nayak AK, Ahmad SA, Beg S, Ara TJ, Hasnain MS, Inamuddin, et al. 12 - Drug delivery: Present, past, and future of medicine. In: Applications of nanocomposite materials in drug delivery: Woodhead Publishing; 2018. p. 255–82.
Bansal S, Beg S, Asthana A, Garg B, Asthana GS, Kapil R, et al. QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride. Drug Deliv. 2014;23(2):437–51.
Turker S, Onur E, Ozer Y. Nasal route and drug delivery systems. Pharm World Sci. 2004;26(3):137–42.
Agu RU. Challenges in nasal drug absorption: how far have we come? Ther Deliv. 2016;7(7):495–510.
Merkus FW, Verhoef JC, Schipper NG, Marttin E. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev. 1998;29(1–2):13–38.
Chaturvedi M, Kumar M, Pathak K. A review on mucoadhesive polymer used in nasal drug delivery system. J Adv Pharm Technol Res. 2011;2(4):215–22.
Varde NK, Pack DW. Microspheres for controlled release drug delivery. Expert Opin Biol Ther. 2004;4(1):35–51.
Türker S, Onur E. Öz e r Y. nasal route and drug delivery systems. Pharm World Sci. 2004;26:137–42.
Borghi C. Lercanidipine in hypertension. Vasc Health Risk Manag. 2005;1(3):173–82.
Grassi G, Robles NR, Seravalle G, Fici F. Lercanidipine in the management of hypertension: an update. J Pharmacol Pharmacother. 2017;8(4):155–65.
Shaikh F, Patel M, Surti N, Patel V. Preparation and characterization of lercanidipine hydrochloride inclusion complex with β-cyclodextrin and effect of complexation on solubility and dissolution. Res J Pharm Tech. 2017;10:1041–7.
Jeong HK, Park JY, Kim SY, Cha SR, Lee SE, Jang NK, et al. Dissolution properties of Lercanidipine solid dispersion manufactured water – soluble polymer PVP K-30. Polymer Korea. 2016;40(1):33–9.
Beg S, Hasnain MS. Pharmaceutical quality by design: principles and applications: Academic Press; 2019.
Beg S, Rahman M, Panda SS. Pharmaceutical QbD: omnipresence in the product development lifecycle. Eur Pharm Rev. 2017;22(1):58–64.
Beg S, Hasnain MS, Rahman M, Swain S. Chapter 1 - Introduction to Quality by Design (QbD): Fundamentals, Principles, and Applications. In: Beg S, Hasnain MS, editors. Pharmaceutical Quality by Design: Academic Press; 2019. p. 1–17.
Singh B, Beg S, Raza K. Developing “optimized” drug products employing “designed” experiments. Chem Ind Digest. 2013;23:70–6.
Beg S, Rahman M, Kohli K. Quality-by-design approach as a systematic tool for the development of nanopharmaceutical products. Drug Discov Today. 2019;24(3):717–25.
Singh B, Beg S. Quality by design in product development life cycle. Chron Pharmabiz. 2013;22:72–9.
Nayak AK, Ahmed SA, Beg S, Tabish M, Hasnain MS. Chapter 18 - Application of Quality by Design for the Development of Biopharmaceuticals. In: Beg S, Hasnain MS, editors. Pharmaceutical Quality by Design: Academic Press; 2019. p. 399–411.
Beg S, Swain S, Rahman M, Hasnain MS, Imam SS. Chapter 3 - Application of Design of Experiments (DoE) in Pharmaceutical Product and Process Optimization. In: Beg S, Hasnain MS, editors. Pharmaceutical Quality by Design: Academic Press; 2019. p. 43–64.
Swain S, Jena BR, Madugula D, Beg S, Hasnain MS. Chapter 6 - Application of Quality by Design Paradigms for Development of Solid Dosage Forms. In: Pharmaceutical Quality by Design: Academic Press; 2019. p. 109–30.
Hasnain MS, Ahmed SA, Beg S, Ansari MT, Nayak AK. Chapter 15 - Quality by Design Approach for Development of Multiparticulate Drug Delivery Systems. In: Beg S, Hasnain MS, editors. Pharmaceutical Quality by Design: Academic Press; 2019. p. 351–65.
Hoa LTM, Chi NT, Triet NM, Nhan LNT, Chien DM. Preparation of drug nanoparticles by emulsion evaporation method. J Phys. 2009;187:012047.
Santhi K, Dhanraj S, Koshy M, Ponnusankar S, Suresh B. Study of biodistribution of methotrexate loaded bovine serum albumin microsphers in mice. Drug Dev Ind Pharm. 2000;26:1293–6.
Swain S, Behera UA, Beg S, Sruti J, Patro Ch N, Dinda SC, et al. Design and characterization of enteric-coated controlled release mucoadhesive microcapsules of Rabeprazole sodium. Drug Dev Ind Pharm. 2012;39(4):548–60.
Mihaljica S, Radulović D, Trbojević J. Determination of lercanidipine hydrochloride and its impurities in tablets. Chromatographia. 2005;61(1):25–9.
Pereswetoff-Morath L. Microspheres as nasal drug delivery systems. Adv Drug Deliv Rev. 1998;29(1–2):185–94.
Schall R, Luus HG. Comparison of absorption rates in bioequivalence studies of immediate release drug formulations. Int J Clin Pharmacol Ther Toxicol. 1992;30:153–9.
Endrenyi L, Yan W. Variation of Cmax and Cmax/AUC in investigations of bioequivalence. Int J Clin Pharmacol Ther Toxicol. 1993;31:184–9.