Optimization of Gastroretentive Delayed Release Drug Delivery using Design of Experiment Approach
Abstract
Gastroretentive drug delivery with delayed release of propranolol hydrochloride for chronotherapy of hypertension was formulated. The drug delivery in the form of compression coated tablet was developed using Indian Pharmacopoeia grade hydroxypropyl methyl cellulose K100M and carbopol 934P as matrix forming polymers and polyvinyl pyrrolidone K30 as channelling agent. Drug-excipient compatibility study revealed no interaction between drug and the excipients. Prepared tablets were evaluated for floating lag time, total floating time and lag time before drug release. Drug delivery was optimized by using 32 full factorial design. The concentrations of matrix forming polymers were selected as independent variables whereas lag time before drug release, drug release at 8, 12 and 20 h were selected as response variables. Tablets of optimized batch F5 containing 25% hydroxypropyl methyl cellulose K100M and 9% polyvinyl pyrrolidone K30 exhibited the maximum similarity with predicted drug release profile for an ideal formulation with similarity factor of 80.69. The lag time before drug release (5 h), drug release at 8 h (27.39%), 12 h (49.48%) and 20 h (86.69%) of optimized batch were close to predicted drug release profile for an ideal formulation. Drug release from optimized batch followed zero order kinetics with super case II transport. Optimized formulation was stable for 1 mo at environmental conditions of 40±2°C temperature and 75±5% relative humidity. Prepared drug delivery of propranolol hydrochloride may be useful to provide sustained drug release for 24 h at the site of absorption for chronotherapy of hypertension.
Keywords:
Propranolol hydrochloride, gastroretentive pulsatile drug delivery, chronotherapy, design of experiment, full factorial designDOI
https://doi.org/10.25004/IJPSDR.2022.140412References
Lemmer B. Chonopharmacokinetics: Implications for drug treatment. Journal of Pharmacy and Pharmacology. 1999;51:887-90.
Ghimire M, McInnes FJ, Watson DG, Mullen AB, Stevens HN. In vitro in vivo correlation of pulsatile drug release from press coated tablet formulations: A pharmacoscintigraphic study in the beagle dog. European Journal of Pharmaceutics and Biopharmaceutics. 2007;67:515-23.
Udupa N, Gupta PD. Concepts in chonopharmacology. 1st Edn. Shyam Prakashan Publishers, Jaipur, India 2009:P.92-108.
Fox KM, Mulcahy DA. Circadian rhythms in cardiovascular diseases. Postgraduate Medical Journal. 1991;67 Suppl 3:S33-6.
Millar-Craig MW, Bishop CN, Raftery EB. Circadian variation of blood pressure. Lancet. 1978;1:795-97.
Hoffman A, Stepensky D, Lavy E, Eyal S, Klausner E, Friedman M. Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms. International Journal of Pharmacutics. 2004;277:141-53.
Badve SS, Sher P, Korde A, Pawar AP. Development of hollow porous calcium pectinate beads for floating-pulsatile drug delivery. European Journal of Pharmaceutics and Biopharmaceutics. 2007;65:85-93.
Krögel I, Bodmeier R. Floating or pulsatile drug delivery systems based on coated effervescent cores. International Journal of Pharmacutics. 1999;187:175-84.
Zaman M, Akhtar F, Baseer A, Hasan SMF, Aman W, Khan A, et al. Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach. Pakastn Journal of Pharmaceutical Sciences. 2021;34:57-63.
Momin S, Khan S, Ghadage DM, Yadav AV, Wagh A. Formulation and evaluation of bilayer tablets of propranolol hydrochloride. Journal of Drug Delivery and Therapeutics. 2017;7:50-57.
Jagdale SC, Agavekar AJ, Pandya SV, Kuchekar BS, Chabukswar AR. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride. AAPS Pharmaceutical Science and Technology. 2009;10:1071-79.
Srikanth MV, Uhumwangho MU, Rao NS, Sunil SA, Ram BJ, Murthy KVR. Formulation and evaluation of gastro retentive floating drug delivery system for Propranolol HCl. Journal of Pharmacy and Bioallied Science. 2011;8:1339-48.
Srikanthn MV, Rao NS, Ambedkar SS, Battu JR, Kolapalli VRM. Statistical design and evaluation of a propranolol HCl gastric floating tablet. Acta Pharmaceutica Sinica B. 2012;2:60-69.
Safhi MM. Formulation and in vitro evaluation of sustained release intragastric tablets of propranolol hydrochloride using natural polymer. Journal of Pharmaceutical and Biomedical Science. 2010;10:1-6.
Garrepally P, Bontha VK, Gonugunta CSR, Vemula SK, Chilukala S, Yarlaga S, et al. Intragastric floating drug delivery system of propranolol hydrochloride containing natural resin mangifera indica. Journal of Pharmacy Practice. 2011;1:4-10.
Pandey S, Devmurari V, Shukla P, Rathanand M. Development and in vitro evaluation of propranolol hydrochloride based gastro-retentive floating tablet. Scholars Research Library: Der Pharmacia Lettre. 2010;2:75-86.
Wakde PH, Kasliwal RH, Mane SB. Design and fabrication of gastroretentive bilayer floating tablet of Propranolol HCl using natural polymer. International Journal of Pharmaceutical Science and Research. 2013;4:4715-28.
Djuris J, Medarevic D, Krsti M, Vasiljevic I, Masic I, Ibric S. Design space approach in optimization of fluid bed granulation and tablets compression process. Science World Journal. 2012; Article ID 185085:doi.org/10.1100/2012/185085.
Krstic M, Duris J, Petrovic O, Lazarevic N, Cvijic S, Ibric S. Application of the melt granulation technique in the development of self-emulsifying tablets with immediate release of carbamazepine. Journal of Drug Delivery Science and Technology. 2017;39:467-74.
Krstic M, Lukic I, Busatlic A, Lazarevic N, Vasiljevic D. Solid dispersions with carbamazepine: optimization of formulation, characterization and examination of long-term stability. Chemical Industry. 2018;72:191-204.
Krstic M, Ibric S. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine. Chemical Industry. 2016;70:525-37.
Krstic M, Razic SS, Djekic LM, Dobricic VD, Momcilovic MA, Vasiljevic DD, et al. Application of a mixture experimental design in the optimization of the formulation of solid self-emulsifying drug delivery systems containing carbamazepine. Latin American Journal of Pharmacy. 2015;34:885-94.
Krstic M, Razic S, Vasiljevic D, Spasojevic D, Ibric S. Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis. Journal of Serbian Chemical Society. 2015;80:209-22.
Zhu S, Hong M, Liu C, Pei Y. Application of Box-Behnken design in understanding the quality of genistein self-nanoemulsified drug delivery systems and optimizing its formulation. Pharmaceutical Development and Technology. 2009;14: 642-9.
Reynolds JEF. Martindale: The Extra Pharmacopoeia, 31st Edn. Royal Pharmaceutical Society, London 1996:P.933-36.
Robinson JR, Eriksen SP. Theoretical formulation of sustained dosage forms. Journal of Pharmaceutical Science. 1966;55:1254-63.
Indian Pharmacopoeia, The Indian Pharmacopoeial Commission, Ministry of Family Welfare, Ghaziabad, India 2007;3:996-97.
Flese EF, Hugen TA. Preformulation. In The theory and practice of industrial Pharmacy; 4th Edn; Varghese publishing house, Mumbai 1987: P.171-293.
Wells JI, Aulton ME. Preformulation. In Pharmaceutics: the science of dosage form design; 2nd Edn; Churchill Livingstone, London 2002:P.223-53.
Cooper J, Gun C. Powder flow and compaction. In Tutorial Pharmacy; CBS Publishers and Distributors, New Delhi, India 1986:P.211-33.
Martin A. Micromeritics. In Physical Pharmacy; 4th Edn; B.I. Waverly Pvt. Ltd., New Delhi, India 1997:P.423-54.
Xiaoqiang X, Minjie S, Feng Z, Yiqiao H. Floating matrix dosage form for phenoporlamine hydrochloride based on gas forming agent: in vitro and in vivo evaluation in healthy volunteers. International Journal of Pharmaceutics. 2006;310:139-45.
Sawada T, Sako K, Fukui M, Yokohama S, Hayashi A. A new index, the core erosion ratio, of compression-coated timed-release tablets predicts the bioavailability of acetaminophen. International Journal of Pharmaceutics. 2003;265:55-63.
Higuchi T. Mechanism of sustained action mediation, theoretical analysis of rate of release of solid drugs dispersed in solid matrices. Journal of Pharmaceutical Science. 1963;52:1145-49.
Hixon AW, Crowell JH. Dependence of reaction velocity upon surface and agitation. Industrial Engineering and Chemical Research. 1931;23:923-31.
Korsemeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics. 1983;15:25-35.
Published

