Orodispersible Carbamazepine/Hydroxypropyl-β-Cyclodextrin Tablets Obtained by Direct Compression with Five-in-One Co-processed Excipients.
F-Melt® type C
Prosolv® ODT G2
carbamazepine/hydroxypropyl-β-cyclodextrin complexes
direct compression
orally disintegrating tablets
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
02 Jan 2020
02 Jan 2020
Historique:
received:
27
07
2019
accepted:
12
11
2019
entrez:
4
1
2020
pubmed:
4
1
2020
medline:
28
3
2020
Statut:
epublish
Résumé
The development of orodispersible tablets (ODTs) for poorly soluble and poorly flowable drugs via direct compression is still a challenge. This work aimed to develop ODTs of poorly soluble drugs by combining cyclodextrins that form inclusion complexes to improve wetting and release properties, and directly compressible co-processed excipients able to promote rapid disintegration and solve the poor flowability typical of inclusion complexes. Carbamazepine (CBZ) and hydroxypropyl-β-cyclodextrin (HPβCD) were used, respectively, as a model of a poorly soluble drug with poor flowability and as a solubilizing agent. Specifically, CBZ-an antiepileptic and anticonvulsant drug-may benefit from the studied formulation approach, since some patients have swallowing difficulties or fear of choking and are non-cooperative. Prosolv® ODT G2 and F-Melt® type C were the studied five-in-one co-processed excipients. The complex was prepared by kneading. Flow properties of all materials and main properties of the tablets were characterized. The obtained results showed that ODTs containing CBZ/HPβCD complex can be prepared by direct compression through the addition of co-processed excipients. The simultaneous use of co-processing and cyclodextrin technologies rendered ODTs with an in vitro disintegration time in accordance with the European Pharmacopoeia requirement and with a fast and complete drug dissolution. In conclusion, the combination of five-in-one co-processed excipients and hydrophilic cyclodextrins may help addressing the ODT formulation of poorly soluble drugs with poor flowability, by direct compression and with desired release properties.
Identifiants
pubmed: 31897724
doi: 10.1208/s12249-019-1579-5
pii: 10.1208/s12249-019-1579-5
doi:
Substances chimiques
Anticonvulsants
0
Excipients
0
Tablets
0
2-Hydroxypropyl-beta-cyclodextrin
1I96OHX6EK
Carbamazepine
33CM23913M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
39Références
Conceição J, Adeoye O, Cabral-Marques HM, Lobo JMS. Cyclodextrins as drug carriers in pharmaceutical technology: the state of the art. Curr Pharm Des. 2018;24(13):1405–33.
pubmed: 29256342
Narvekar M, Xue HY, Eoh JY, Wong HL. Nanocarrier for poorly water-soluble anticancer drugs—barriers of translation and solutions. AAPS PharmSciTech. 2014;15(4):822–33.
pubmed: 24687241
pmcid: 4113620
Jansook P, Ogawa N, Loftsson T. Cyclodextrins: structure, physicochemical properties and pharmaceutical applications. Int J Pharm. 2018;535(1–2):272–84.
pubmed: 29138045
Salústio PJ, Pontes P, Conduto C, Sanches I, Carvalho C, Arrais J, et al. Advanced technologies for oral controlled release: cyclodextrins for oral controlled release. AAPS PharmSciTech. 2011;12(4):1276–92.
pubmed: 21948320
pmcid: 3225529
Jacob S, Nair AB. Cyclodextrin complexes: perspective from drug delivery and formulation. Drug Dev Res. 2018;79(5):201–17.
pubmed: 30188584
Conceição J, Adeoye O, Cabral-Marques HM, Lobo JMS. Cyclodextrins as excipients in tablet formulations. Drug Discov Today. 2018;23(6):1274–84.
pubmed: 29689302
Adeoye O, Cabral-Marques H. Cyclodextrin nanosystems in oral drug delivery: a mini review. Int J Pharm. 2017;531(2):521–31.
pubmed: 28455134
Loftsson T, Saokham P, Sá Couto AR. Self-association of cyclodextrins and cyclodextrin complexes in aqueous solutions. Int J Pharm. 2019;560:228–34.
pubmed: 30771468
Conceição J, Farto-Vaamonde X, Goyanes A, Adeoye O, Concheiro A, Cabral-Marques H, et al. Hydroxypropyl-β-cyclodextrin-based fast dissolving carbamazepine printlets prepared by semisolid extrusion 3D printing. Carbohydr Polym. 2019;221:55–62.
pubmed: 31227167
European Pharmacopoeia, 9th edition. Strasbourg, France: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe; 2016.
Cilurzo F, Musazzi UM, Franzé S, Selmin F, Minghetti P. Orodispersible dosage forms: biopharmaceutical improvements and regulatory requirements. Drug Discov Today. 2018;23(2):251–9.
pubmed: 29030242
Visser JC, Woerdenbag HJ, Hanff LM, Frijlink HW. Personalized medicine in pediatrics: the clinical potential of orodispersible films. AAPS PharmSciTech. 2017;18(2):267–72.
pubmed: 27044380
Slavkova M, Breitkreutz J. Orodispersible drug formulations for children and elderly. Eur J Pharm Sci. 2015;75:2–9.
pubmed: 25736528
Petrovick GF, Kleinebudde P, Breitkreutz J. Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: influence of process parameters on tablet properties. Eur J Pharm Biopharm. 2018;122:137–45.
pubmed: 29106946
Zeng F, Wang L, Zhang W, Shi K, Zong L. Formulation and in vivo evaluation of orally disintegrating tablets of clozapine/hydroxypropyl-β-cyclodextrin inclusion complexes. AAPS PharmSciTech. 2013;14(2):854–60.
pubmed: 23649995
pmcid: 3666014
Mangal S, Meiser F, Morton D, Larson I. Particle engineering of excipients for direct compression: understanding the role of material properties. Curr Pharm Des. 2015;21(40):5877–89.
pubmed: 26446468
Bowles BJ, Dziemidowicz K, Lopez FL, Orlu M, Tuleu C, Edwards AJ, et al. Co-processed excipients for dispersible tablets—part 1: manufacturability. AAPS PharmSciTech. 2018;19(6):2598–609.
pubmed: 29916193
Patel S, Kaushal AM, Bansal AK. Compression physics in the formulation development of tablets. Crit Rev Ther Drug Carrier Syst. 2006;23(1):1–65.
pubmed: 16749898
Dziemidowicz K, Lopez FL, Bowles BJ, Edwards AJ, Ernest TB, Orlu M, et al. Co-processed excipients for dispersible tablets—part 2: patient acceptability. AAPS PharmSciTech. 2018;19(6):2646–57.
pubmed: 29943280
Krupa A, Jachowicz R, Pędzich Z, Wodnicka K. The influence of the API properties on the ODTs manufacturing from co-processed excipient systems. AAPS PharmSciTech. 2012;13(4):1120–9.
pubmed: 22941425
pmcid: 3513440
Siow CRS, Tang DS, Heng PWS, Chan LW. Probing the impact of HPMC viscosity grade and proportion on the physical properties of co-freeze-dried mannitol-HPMC tableting excipients using multivariate analysis methods. Int J Pharm. 2019;556:246–62.
pubmed: 30529666
Assaf SM, Subhi Khanfar M, Bassam Farhan A, Said Rashid I, Badwan AA. Preparation and characterization of co-processed starch/MCC/chitin hydrophilic polymers onto magnesium silicate. Pharm Dev Technol. 2019;24(6):761–74.
pubmed: 30888873
Rathod P, Mori D, Parmar R, Soniwala M, Chavda J. Co-processing of cefuroxime axetil by spray drying technique for improving compressibility and flow property. Drug Dev Ind Pharm. 2019;45(5):767–74.
pubmed: 30722705
Saha S, Shahiwala AF. Multifunctional coprocessed excipients for improved tabletting performance. Expert Opin Drug Deliv. 2009;6(2):197–208.
pubmed: 19239391
Rojas J, Buckner I, Kumar V. Co-proccessed excipients with enhanced direct compression functionality for improved tableting performance. Drug Dev Ind Pharm. 2012;38(10):1159–70.
pubmed: 22966909
Mirani AG, Patankar SP, Borole VS, Pawar AS, Kadam VJ. Direct compression high functionality excipient using coprocessing technique: a brief review. Curr Drug Deliv. 2011;8(4):426–35.
pubmed: 21235470
Al-Khattawi A, Mohammed AR. Challenges and emerging solutions in the development of compressed orally disintegrating tablets. Expert Opin Drug Discovery. 2014;9(10):1109–20.
Al-Khattawi A, Mohammed AR. Compressed orally disintegrating tablets: excipients evolution and formulation strategies. Expert Opin Drug Deliv. 2013;10(5):651–63.
pubmed: 23387409
Gierbolini J, Giarratano M, Benbadis SR. Carbamazepine-related antiepileptic drugs for the treatment of epilepsy—a comparative review. Expert Opin Pharmacother. 2016;17(7):885–8.
pubmed: 26999402
Higuchi T, Connors KA. Phase solubility techniques. Adv Anal Chem Instrum. 1965;4:117–212.
United States Pharmacopeia (USP) 41 - National Formulary (NF) 36. Rockville, United States of America: The United States Pharmacopeial Convention; 2017.
Loftsson T, Brewster ME. Cyclodextrins as functional excipients: methods to enhance complexation efficiency. J Pharm Sci. 2012;101(9):3019–32.
pubmed: 22334484
Kleptose®: betacyclodextrins and hydroxypropyl betacyclodextrins: Roquette; 2006.
Conceição J, Adeoye O, Cabral-Marques HM, Sousa Lobo JM. Hydroxypropyl-β-cyclodextrin and β-cyclodextrin as tablet fillers for direct compression. AAPS PharmSciTech. 2018;19(6):2710–8.
pubmed: 29978292
Conceição J, Teixeira C, Sousa G, Simões AM, Amorim A, Sá B, et al. Tablet machine instrumentation: influence of lubricants on the lubrication efficiency and compaction profiles. Arh Farm. 2016;66:111–2.
Conceição J, Sousa G, Teixeira C, Simões AM, Sá B, Sousa Lobo JM. Influence of lubricants on tabletting and drug release characteristics. In: 10th world meeting on pharmaceutics, biopharmaceutics and pharmaceutical technology; Glasgow: APV, APGI and A.D.R.I.T.E.L.F; 2016.
Moqbel HA, ElMeshad AN, El-Nabarawi MA. A pharmaceutical study on chlorzoxazone orodispersible tablets: formulation, in-vitro and in-vivo evaluation. Drug Deliv. 2016;23(8):2998–3007.
pubmed: 26828616
Kohlmann P, Stillhart C, Kuentz M, Parrott N. Investigating oral absorption of carbamazepine in pediatric populations. AAPS J. 2017;19(6):1864–77.
pubmed: 28971365
Chandrasekaran P, Kandasamy R. Development of extended-release oral flexible tablet (ER-OFT) formulation for pediatric and geriatric compliance: an age-appropriate formulation. AAPS PharmSciTech. 2017;18(7):2394–409.
pubmed: 28138820
European Medicines Agency (EMA), Committee for Human Medicinal Products (CHMP). Background review for cyclodextrins used as excipients. London; 2014. https://www.ema.europa.eu/en/documents/report/background-review-cyclodextrins-used-excipients-context-revision-guideline-excipients-label-package_en.pdf .
Kou W, Cai C, Xu S, Wang H, Liu J, Yang D, et al. In vitro and in vivo evaluation of novel immediate release carbamazepine tablets: complexation with hydroxypropyl-β-cyclodextrin in the presence of HPMC. Int J Pharm. 2011;409(1–2):75–80.
pubmed: 21371541
Koester LS, Xavier CR, Mayorga P, Bassani VL. Influence of beta-cyclodextrin complexation on carbamazepine release from hydroxypropyl methylcellulose matrix tablets. Eur J Pharm Biopharm. 2003;55(1):85–91.
pubmed: 12551708
Loh GOK, Tan YTF, Peh K-K. Enhancement of norfloxacin solubility via inclusion complexation with β-cyclodextrin and its derivative hydroxypropyl-β-cyclodextrin. Asian J Pharm Sci. 2016;11(4):536–46.
Mura P. Analytical techniques for characterization of cyclodextrin complexes in the solid state: a review. J Pharm Biomed Anal. 2015;113:226–38.
pubmed: 25743620
Jain AS, Date AA, Pissurlenkar RR, Coutinho EC, Nagarsenker MS. Sulfobutyl ether(7) β-cyclodextrin (SBE(7) β-CD) carbamazepine complex: preparation, characterization, molecular modeling, and evaluation of in vivo anti-epileptic activity. AAPS PharmSciTech. 2011;12(4):1163–75.
pubmed: 21918921
pmcid: 3225538
Katzhendler I, Azoury R, Friedman M. Crystalline properties of carbamazepine in sustained release hydrophilic matrix tablets based on hydroxypropyl methylcellulose. J Control Release. 1998;54(1):69–85.
pubmed: 9741905
Medarević D, Kachrimanis K, Djurić Z, Ibrić S. Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin. Eur J Pharm Sci. 2015;78:273–85.
pubmed: 26255049
Salústio PJ, Cabral-Marques HM, Costa PC, Pinto JF. Comparison of ibuprofen release from minitablets and capsules containing ibuprofen: β-cyclodextrin complex. Eur J Pharm Biopharm. 2011;78(1):58–66.
pubmed: 21195175
Salústio PJ, Pinto JF, Costa PC, Cabral-Marques HM. Release profiles of indometacin in β-cyclodextrin complexes from HPMC capsules. J Incl Phenom Macrocycl Chem. 2013;75:101–9.
Conceição J, Sá B, Vaz Q, Mesquita P, Sousa G, Sousa Lobo JM. Effect of superdisintegrants on dissolution rate and disintegration time. Arh Farm. 2016;66:109–10.
Guidance for industry: orally disintegrating tablets: Food and Drug Administration (FDA); 2008.
Rao NGR, Patel T, Gandhi S. Development and evaluation of carbamazepine fast dissolving tablets prepared with a complex by direct compression technique. Asian J Pharm. 2009;3(2):97–103.
Arima H, Higashi T, Motoyama K. Improvement of the bitter taste of drugs by complexation with cyclodextrins: applications, evaluations and mechanisms. Ther Deliv. 2012;3(5):633–44.
pubmed: 22834407