Quality by design approach for nifedipine-adsorbed fluorite-loaded calcium-low methoxy pectin beads to impart chronotherapy: in vitro and in vivo assessment.
Uložené v:
| Názov: | Quality by design approach for nifedipine-adsorbed fluorite-loaded calcium-low methoxy pectin beads to impart chronotherapy: in vitro and in vivo assessment. |
|---|---|
| Autori: | Jagtap RS; Department of Pharmaceutics, Vijayrao Naik College of Pharmacy, Shirval-Kankavli Sindhudurg, Maharashtra, 416620, India. rajeshjagtap0807@gmail.com., Mohite SK; Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy Kasegaon, Sangli, Maharashtra, India., Jagtap SR; Late Adv. Dadasaheb Chavan Memorial Institute of Pharmacy, Malwadi (Masur), Maharashtra, India., Nadaf SJ; Department of Pharmaceutics, Bharati Vidyapeeth College of Pharmacy, Palus, Sangli, Maharashtra, 416310, India., Mali SS; Department of Pharmaceutics (PG), Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416 013, India., Sankpal PS; Department of Pharmaceutics, Bharati Vidyapeeth College of Pharmacy, Palus, Sangli, Maharashtra, 416310, India., Singh S; Office of Research Administration, Chiang Mai University, Chiang Mai, 50200, Thailand. sudarshan.s@cmu.ac.th.; Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand. sudarshan.s@cmu.ac.th. |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2025 Dec; Vol. 398 (12), pp. 18023-18034. Date of Electronic Publication: 2025 Jun 28. |
| Spôsob vydávania: | Journal Article |
| Jazyk: | English |
| Informácie o časopise: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin, New York, Springer Verlag. |
| Výrazy zo slovníka MeSH: | Pectins*/chemistry , Nifedipine*/administration & dosage , Nifedipine*/pharmacokinetics , Nifedipine*/chemistry , Calcium Compounds*/chemistry , Calcium Compounds*/administration & dosage , Silicates*/chemistry , Silicates*/administration & dosage , Calcium Channel Blockers*/administration & dosage , Calcium Channel Blockers*/pharmacokinetics , Calcium Channel Blockers*/chemistry, Animals ; Drug Liberation ; Male ; Drug Delivery Systems ; Drug Chronotherapy ; Adsorption ; Delayed-Action Preparations ; Rats ; Drug Carriers/chemistry ; Solubility ; Biological Availability |
| Abstrakt: | Majority of conventional oral delivery fails to maintain therapeutic concentration of drugs at site of action due to fast gastric-emptying time. Therefore, to overcome these inherent limitations and to improve pharmacokinetic parameters, a porous calcium silicate, fluorite (Florite RE®: FLR) and low methoxy (LM) pectin-based floating-pulsatile drug delivery system was developed for engineered specific drug release of nifedipine (NFD). FLR was investigated as multifaceted acting agent to act as solublizer and to impart pulsatile release. FLR-based NFD-loaded floating-pulsatile pectin beads were prepared using ionotropic gelation technique and optimized via 3 2 factorial design. Concentration of FLR-adsorbed NFD ( INLINEMATH ) and LM pectin ( INLINEMATH ) was used as independent variables, while lag time ( INLINEMATH ) and floating time ( INLINEMATH ) were tested as response variables. Prepared beads were evaluated for entrapment efficiency, mechanical strength, floating time, in vitro dissolution, and in vivo pharmacokinetic studies. Optimized formulation (F4) showed lag time of 6.00 ± 0.21 h and released ~ 100% of drug from beads within 1.5 h after a lag time. Furthermore, INLINEMATH showed significant positive effect on INLINEMATH and INLINEMATH , whereas INLINEMATH exhibited significant positive and negative effect on INLINEMATH and INLINEMATH respectively. Additionally, FLR-NFD-based beads demonstrated improvement in bioavailability of drug tested by 1.90-folds, compared to its native form-loaded beads. This two-stage approach could emerge as a promising approach to get relief from cardiac disorders that follows biological clock. (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
| References: | Albadry AA, Ali WK, Al-saady FA (2017) Formulation and evaluation of prochlorperazine maleate sustained release floating tablet. Int J Pharm Pharm Sci 9:89. https://doi.org/10.22159/ijpps.2017v9i2.15665. (PMID: 10.22159/ijpps.2017v9i2.15665) Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ (2021) Advances in oral drug delivery. Front Pharmacol 12. https://doi.org/10.3389/fphar.2021.618411 . Ankita W (2024) |Review. Int J of Pharm Sci 2:1075–1091. https://doi.org/10.5281/zenodo.13955626. (PMID: 10.5281/zenodo.13955626) Ansari M, Sadarani B, Majumdar A (2019) Colon targeted beads loaded with pterostilbene: Formulation, optimization, characterization and in vivo evaluation. Saudi Pharma J 27:71–81. https://doi.org/10.1016/j.jsps.2018.07.021. (PMID: 10.1016/j.jsps.2018.07.021) Aydin Z, Akbug J (1996) Preparation and evaluation of pectin beads. Int J Pharma 137(1):133–136. https://doi.org/10.1016/0378-5173(95)04458-2. (PMID: 10.1016/0378-5173(95)04458-2) Badve SS, Sher P, Korde A, Pawar AP (2007) Development of hollow/porous calcium pectinate beads for floating-pulsatile drug delivery. Eur J Pharm Biopharm 65:85–93. https://doi.org/10.1016/j.ejpb.2006.07.010. (PMID: 10.1016/j.ejpb.2006.07.01016971097) Bera H, Boddupalli S, Nandikonda S, Kumar S, Nayak AK (2015) Alginate gel-coated oil-entrapped alginate-tamarind gum-magnesium stearate buoyant beads of risperidone. Int J Biol Macromol 78:102–111. https://doi.org/10.1016/j.ijbiomac.2015.04.001. (PMID: 10.1016/j.ijbiomac.2015.04.00125861741) Bhai Gajapathy D, Ubaidulla U, Sinha P, Rathnam G. (n.d.) Gastroretentive floating beads-an emerging trend in drug delivery. Int J Pharma Res Appli 7:1510. https://doi.org/10.35629/7781-070215101520. Bharti C, Nagaich U, Pandey J, Jain S, Jain N. Development of nitazoxanide-loaded colon-targeted formulation for intestinal parasitic infections: centre composite design-based optimization and characterization. Futur J Pharm Sci 2020;6. https://doi.org/10.1186/s43094-020-00130-1 . Bhutani U, Basu T, Majumdar S (2021) Oral drug delivery: conventional to long acting new-age designs. Eur J Pharm Biopharm 162:23–42. https://doi.org/10.1016/j.ejpb.2021.02.008. (PMID: 10.1016/j.ejpb.2021.02.00833631319) Bi Y, Lv B, Li L, Lee RJ, Xie J, Qiu Z, et al (2020) A liposomal formulation for improving solubility and oral bioavailability of nifedipine. Molecules 25. https://doi.org/10.3390/molecules25020338 . Bindhani S, Mohapatra S, Kar RK (2020) Preparation, characterization and stability studies of solid self emulsifying drug delivery system of nifedipine. Int J Appl Pharma 12:94–102. https://doi.org/10.22159/ijap.2020v12i2.36406 . Cerutti JP, Quevedo MA, Buhlman N, Longhi MR, Zoppi A (2019) Synthesis and characterization of supramolecular systems containing nifedipine, β-cyclodextrin and aspartic acid. Carbohydr Polym 205:480–487. https://doi.org/10.1016/j.carbpol.2018.10.038. (PMID: 10.1016/j.carbpol.2018.10.03830446131) Das S, Kaur S, Rai VK (2021) Gastro-retentive drug delivery systems: a recent update on clinical pertinence and drug delivery. Drug Deliv Transl Res 11:1849–1877. https://doi.org/10.1007/s13346-020-00875-5. (PMID: 10.1007/s13346-020-00875-533403646) Günter EA, Markov PA, Melekhin AK, Belozerov VS, Martinson EA, Litvinets SG et al (2018) Preparation and release characteristics of mesalazine loaded calcium pectin-silica gel beads based on callus cultures pectins for colon-targeted drug delivery. Int J Biol Macromol 120:2225–2233. https://doi.org/10.1016/j.ijbiomac.2018.07.078. (PMID: 10.1016/j.ijbiomac.2018.07.07830012483) Hanada M, Jermain SV, Williams RO (2018) Enhanced dissolution of a porous carrier-containing ternary amorphous solid dispersion system prepared by a hot melt method. J Pharm Sci 107:362–371. https://doi.org/10.1016/j.xphs.2017.09.025. (PMID: 10.1016/j.xphs.2017.09.02528989021) Huanbutta K, Sangnim T (2019) Design and development of zero-order drug release gastroretentive floating tablets fabricated by 3D printing technology. J Drug Deliv Sci Technol 52:831–837. https://doi.org/10.1016/j.jddst.2019.06.004. (PMID: 10.1016/j.jddst.2019.06.004) Huanbutta K, Sriamornsak P, Kittanaphon T, Suwanpitak K, Klinkesorn N, Sangnim T (2021) Development of a zero-order kinetics drug release floating tablet with anti–flip-up design fabricated by 3D-printing technique. J Pharm Investig 51:213–222. https://doi.org/10.1007/s40005-020-00507-7. (PMID: 10.1007/s40005-020-00507-7) Ishak RAH (2015) Buoyancy-generating agents for stomach-specific drug delivery: an overview with special emphasis on floating behavior. 18. https://doi.org/10.18433/j3602k. Jagdale SC, Sali MS, Barhate AL, Kuchekar BS, Chabukswar AR (2013) Formulation, development, and evaluation of floating pulsatile drug delivery system of atenolol. PDA J Pharm Sci Technol 67:214–228. https://doi.org/10.5731/pdajpst.2013.00916. (PMID: 10.5731/pdajpst.2013.0091623752749) Jagtap RS, Doijad RC, Mohite SK (2019) Adsorption of nifedipine on porous calcium silicate for enhancement of solubility and dissolution rate. Res J Pharm Technol 12:1273–1279. https://doi.org/10.5958/0974-360X.2019.00213.0. (PMID: 10.5958/0974-360X.2019.00213.0) Jain D, Raturi R, Jain V, Bansal P, Singh R (2011) Recent technologies in pulsatile drug delivery systems. Biomatter 1:57–65. https://doi.org/10.4161/biom.1.1.17717. (PMID: 10.4161/biom.1.1.17717235077273548250) Jantrawut P, Assifaoui A, Chambin O (2013) Influence of low methoxyl pectin gel textures and in vitro release of rutin from calcium pectinate beads. Carbohydr Polym 97:335–342. https://doi.org/10.1016/j.carbpol.2013.04.091. (PMID: 10.1016/j.carbpol.2013.04.09123911454) Khalifa AZ, Zyad H, Mohammed H, Ihsan K, Alrawi L, Abdullah M et al (2022) Recent advances in remotely controlled pulsatile drug delivery systems. J Adv Pharm Technol Res 13:77–82. https://doi.org/10.4103/japtr.japtr_330_21. (PMID: 10.4103/japtr.japtr_330_21354646649022360) Kulkarni GS, Chaudhary PP, Swamy S (2017) Formulation and evaluation of sustained release floating tablets of an antihypertensive diltiazem. Int J Pharma Sci Nanotechnol 10:3844–52. https://doi.org/10.37285/ijpsn.2017.10.5.5 . Kumar K, Dey A, Pal I, Mandal K, Bhowmick B, Sarkar T (2022) Recent advances in gastroretentive drug delivery systems: a review. Asian J Pharma 16:250. https://doi.org/10.22377/ajp.v16i3.4474. (PMID: 10.22377/ajp.v16i3.4474) Kumar V, Somkuwar S, Singhai AK (2024) A recent update on gastro retentive drug delivery systems. GSC Biol Pharma Sci 27:125–44. https://doi.org/10.30574/gscbps.2024.27.1.0119. (PMID: 10.30574/gscbps.2024.27.1.0119) Lowinger MB, Maier EY, Williams RO, Zhang F (2020) hydrophilic poly(urethanes) are an effective tool for gastric retention independent of drug release rate. J Pharm Sci 109:1967–1977. https://doi.org/10.1016/j.xphs.2020.02.011. (PMID: 10.1016/j.xphs.2020.02.01132087181) Mohite P, Puri A, Munde S, Ade N, Yadav V, Singh S, Datta D (2025) Meticulous standards for bio-relevant method development and validation of in vitro release testing for regenerative topicals: a comprehensive review. Regen Eng Transl Med. https://doi.org/10.1007/s40883-025-00389-x. (PMID: 10.1007/s40883-025-00389-x) Mohsen MMA, Patil AB, Alkanad M, Patil D (2024) Beyond the horizon: recent advances in hot melt extrusion techniques and technologies. Int J Appl Pharma 16:12–21. https://doi.org/10.22159/ijap.2024v16i5.51425. (PMID: 10.22159/ijap.2024v16i5.51425) More M, Nikam M, Kor M, Bhamare M (2023) A new trend in drug delivery system: gastro-retentive floating beads. J Drug Deliv Therap 11. Nadaf SJ, Killedar SG (2018) Curcumin nanocochleates: use of design of experiments, solid state characterization, in vitro apoptosis and cytotoxicity against breast cancer MCF-7 cells. J Drug Deliv Sci Technol 47:337–350. https://doi.org/10.1016/j.jddst.2018.06.026. (PMID: 10.1016/j.jddst.2018.06.026) Ofori-Kwakye K, Mfoafo KA, Kipo SL, Kuntworbe N, El B-G (2016) Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression. Saudi Pharmaceutical Journal 24:82–91. https://doi.org/10.1016/j.jsps.2015.03.005. (PMID: 10.1016/j.jsps.2015.03.00526903772) Pal R, Pandey P, Nogai L, Arushi A, Anand A, Suthar P, et al (2023) The future perspectives and novel approach on gastro retentive drug delivery system (grdds) with current state. J Population Therapeutics Clin Pharmacol. https://doi.org/10.53555/jptcp.v30i17.2852 . Pathak A, Kumar Sharma S (2023) QbD enabled development of press coated tablet of nifedipine: optimization, in-vitro release and stability studies. J Adv Zool 44. Patil H, Vemula SK, Narala S, Lakkala P, Munnangi SR, Narala N et al (2024) Hot-melt extrusion: from theory to application in pharmaceutical formulation—where are we now? AAPS Pharm Sci Tech 25. https://doi.org/10.1208/s12249-024-02749-2 . Qtaitat MA, Zughul MB, Badwan AA (1988) Bromhexine hydrochloride adsorption by some solid excipients used in the formulation of tablets. Drug Dev Ind Pharm 14:415–429. https://doi.org/10.3109/03639048809151874. (PMID: 10.3109/03639048809151874) Rajan S, Sunny SS (2023) Innovations in drug release: a review on gastroretentive drug delivery systems. Int J Advanc Phar Res 28. Ravali V, Balaji P (2024) Pulsatile drug delivery systems: a comprehensive review. Int J Drug Deliv Technol 14:463–71. https://doi.org/10.25258/ijddt.14.1.65. (PMID: 10.25258/ijddt.14.1.65) Sawanny R, Sharma A, Jain S, Mukherjee S, Khamkat P (2023) Gastro retentive drug delivery system: latest approach towards novel drug delivery. Res J Pharm Technol 16:453–8. https://doi.org/10.52711/0974-360X.2023.00077. (PMID: 10.52711/0974-360X.2023.00077) Sharma S, Pawar A (2006) Low density multiparticulate system for pulsatile release of meloxicam. Int J Pharm 313:150–158. https://doi.org/10.1016/j.ijpharm.2006.02.001. (PMID: 10.1016/j.ijpharm.2006.02.00116540268) Sher P, Ingavle G, Ponrathnam S, Pawar AP (2007) Low density porous carrier based conceptual drug delivery system. Microporous Mesoporous Mater 102:290–298. https://doi.org/10.1016/j.micromeso.2007.01.001. (PMID: 10.1016/j.micromeso.2007.01.001) Siddhant Rai, Shaheen Sultana. Gastric retentive drug delivery system and its recent insights : a review. Int J Sci Res Sci Eng Technol 2023:264–81. https://doi.org/10.32628/ijsrset2310127 . Singh SK, Sameer AA (2012) Development and characterization of sublingual tablet of Lisinopril. Asian Pac J Trop Biomed 2(3):S1711–S1719. Singh SS, Singh K (2024) A review on gastro retentive drug delivery system: novel approach with the future perspectives. Int J Pharma Sci. https://doi.org/10.5281/zenodo.11550881. Tarase B, Bobade N, Wankhade V, Atram S, Pande S (2024) A review on pulsatile drug delivery system. Int J of Creative Res Thoughts 12:2320–2882. Tripathi J, Thapa P, Maharjan R, Jeong SH (2019) Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics 11. https://doi.org/10.3390/pharmaceutics11040193 . Vertzoni MV, Reppas C, Archontaki HA (2006) Sensitive and simple liquid chromatographic method with ultraviolet detection for the determination of nifedipine in canine plasma. Anal Chim Acta 573–574:298–304. https://doi.org/10.1016/j.aca.2006.03.037. (PMID: 10.1016/j.aca.2006.03.03717723537) Weerapol Y, Limmatvapirat S, Nunthanid J, Konthong S, Suttiruengwong S, Sriamornsak P (2017) Development and characterization of nifedipine-amino methacrylate copolymer solid dispersion powders with various adsorbents. Asian J Pharm Sci 12:335–343. https://doi.org/10.1016/j.ajps.2017.01.002. (PMID: 10.1016/j.ajps.2017.01.002321043447032161) Weerapol Y, Limmatvapirat S, Nunthanid J, Sriamornsak P (2014) Self-nanoemulsifying drug delivery system of nifedipine: impact of hydrophilic-lipophilic balance and molecular structure of mixed surfactants. AAPS PharmSciTech 15:456–464. https://doi.org/10.1208/s12249-014-0078-y. (PMID: 10.1208/s12249-014-0078-y244525003969497) Weerapol Y, Limmatvapirat S, Takeuchi H, Sriamornsak P (2015) Fabrication of spontaneous emulsifying powders for improved dissolution of poorly water-soluble drugs. Powder Technol 271:100–108. https://doi.org/10.1016/j.powtec.2014.10.037. (PMID: 10.1016/j.powtec.2014.10.037) Wu FY (2024) Nifedipine: an overview of pharmacology, clinical applications, and patient management introduction. Medical Doctor at Virginia Mason Medical Center. 1–5. |
| Contributed Indexing: | Keywords: Calcium silicate; Design of experiment; Low methoxy pectin; Pharmacokinetic; Pulsatile beads |
| Substance Nomenclature: | 89NA02M4RX (Pectins) I9ZF7L6G2L (Nifedipine) 0 (Calcium Compounds) 0 (Silicates) S4255P4G5M (calcium silicate) 0 (Calcium Channel Blockers) 0 (Delayed-Action Preparations) 0 (Drug Carriers) |
| Entry Date(s): | Date Created: 20250628 Date Completed: 20251205 Latest Revision: 20251205 |
| Update Code: | 20251205 |
| DOI: | 10.1007/s00210-025-04330-5 |
| PMID: | 40580312 |
| Databáza: | MEDLINE |
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Majority of conventional oral delivery fails to maintain therapeutic concentration of drugs at site of action due to fast gastric-emptying time. Therefore, to overcome these inherent limitations and to improve pharmacokinetic parameters, a porous calcium silicate, fluorite (Florite RE®: FLR) and low methoxy (LM) pectin-based floating-pulsatile drug delivery system was developed for engineered specific drug release of nifedipine (NFD). FLR was investigated as multifaceted acting agent to act as solublizer and to impart pulsatile release. FLR-based NFD-loaded floating-pulsatile pectin beads were prepared using ionotropic gelation technique and optimized via 3 <sup>2</sup> factorial design. Concentration of FLR-adsorbed NFD ( INLINEMATH ) and LM pectin ( INLINEMATH ) was used as independent variables, while lag time ( INLINEMATH ) and floating time ( INLINEMATH ) were tested as response variables. Prepared beads were evaluated for entrapment efficiency, mechanical strength, floating time, in vitro dissolution, and in vivo pharmacokinetic studies. Optimized formulation (F4) showed lag time of 6.00 ± 0.21 h and released ~ 100% of drug from beads within 1.5 h after a lag time. Furthermore, INLINEMATH showed significant positive effect on INLINEMATH and INLINEMATH , whereas INLINEMATH exhibited significant positive and negative effect on INLINEMATH and INLINEMATH respectively. Additionally, FLR-NFD-based beads demonstrated improvement in bioavailability of drug tested by 1.90-folds, compared to its native form-loaded beads. This two-stage approach could emerge as a promising approach to get relief from cardiac disorders that follows biological clock.<br /> (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
|---|---|
| ISSN: | 1432-1912 |
| DOI: | 10.1007/s00210-025-04330-5 |