Abstract
Hydroxychloroquine is effectively used in the treatment for malaria, lupus erythematosus and rheumatoid arthritis. The study of drug–excipient compatibility is an important tool for the development of safe and effective pharmaceutical forms. The present study describes the use of thermal and nonthermal techniques for evaluating the physicochemical compatibility of hydroxychloroquine with excipients for the development of solid dosage forms, including microcrystalline cellulose, corn starch, mannitol, magnesium stearate and colloidal silicon dioxide. The analytical techniques employed to evaluate the drug and the drug–excipient interactions in solid binary mixtures (1:1 w:w) were differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy (FTIR) and isothermal stress test. Four different formulations were prepared and drug dissolution test was determined by rotating-basket system method in water. Evidence of solid-state interactions of hydroxychloroquine and mannitol, magnesium stearate and colloidal silicon dioxide was observed in the DSC analysis and subsequently confirmed by FTIR; however, no degradation profile was observed by HPLC and no interference was seen in the drug dissolution rate and no change in physicochemical properties of hydroxychloroquine was observed. The combination of techniques is very important to correctly identify drug–excipients incompatibilities in the earliest stage of a formulation design in order to ensure the choice of suitable excipients for the development of stable and effective dosage forms of hydroxychloroquine.
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References
Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutical drug classification: the correlation of in vitro drug product dissolution in the in vivo bioavailability. Pharm Res. 1995;12:413–20.
Verbeeck RK, Junginger HE, Midha KK, Shah VP, Barends DM. Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data: chloroquine phosphate, chloroquine sulfate, and chloroquine hydrochloride. J Pharm Sci. 2005;94:1389–95.
Cook JA, Davit BM, Polli JE. Impact of biopharmaceutics classification system-based biowaivers. Mol Pharm. 2010;7:1539–44.
Bergström CAS, Andersson SBE, Fagerberg JH, Ragnarsson G, Lindahl A. Is the full potential of the biopharmaceutics classification system reached. Eur J Pharm Sci. 2014;57:224–31.
Brazil, Ministério da Saúde - Agência Nacional de Vigilância Sanitária (ANVISA). Resolução - RDC Nº 37, de 3 de agosto de 2011. Dispõe sobre o Guia para isenção e substituição de estudos de biodisponibilidade relativa/bioequivalência e dá outras providências. 2011. http://www.brasilsus.com.br/legislacoes/anvisa/109151-37.html Accessed 15 Feb 2017.
Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Immunol. 2012;42:145–53.
Costedoat-Chalumeau N, Dunogué B, Leroux G, Morel N, Jallouli M, Le Guern V, Piette JC, Brézin AP, Melles RB, Marmor MF. A critical review of the effects of hydroxychloroquine and chloroquine on the eye. Clin Rev Allergy Immunol. 2015;49:317–26.
Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015;23:231–69.
Bharate SS, Bharate SB, Bajaj AN. Incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J Excip Food Chem. 2010;1:3–26.
Chadha R, Bhandari S. Drug-excipient compatibility screening—role of thermoanalytical and spectroscopic techniques. J Pharm Biomed Anal. 2014;87:82–97.
da Silveira LM, Fiorot AB, Xavier TP, Yoshida MI, de Oliveira MA. Drug-excipient compatibility assessment of solid formulations containing meloxicam. Eur J Pharm Sci. 2018;112:146–51.
Veiga A, Oliveira PR, Bernardi LS, Mendes C, Silva MAS, Sangoi MS, Janissek PR, Murakami FS. Solid-state compatibility studies of a drug without melting point: the case of omeprazole sodium. J Therm Anal Calorim. 2018;131:3201–9.
Monajjemzadeh F, Hassanzadeh D, Valizadeh H, Siahi-Shadbad MR, Mojarrad JS, Robertson TA, Roberts MS. Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets. Eur J Pharm Biopharm. 2009;73:404–13.
Thoorens G, Krier F, Leclercq B, Carlin B, Evrard B. Microcrystalline cellulose, a direct compression binder in a quality by design environment—a review. Int J Pharm. 2014;473:64–72.
Ferreira AO. Guia Prático da Farmácia Magistral. 4th ed. Amsterdam: Pharmabooks; 2010.
Teleginski LK, Maciel AB, Mendes C, Silva MAS, Bernardi LS, de Oliveira PR. Fluconazole-excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver. J Therm Anal Calorim. 2015;120:771–81.
Démuth B, Galata DL, Szabó E, Nagy B, Farkas A, Balogh A, Hirsch E, Pataki H, Rapi Z, Bezúr L, Vigh T, Verreck G, Szalay Z, Demeter Á, Marosi G, Nagy ZK. Investigation of deteriorated dissolution of amorphous itraconazole: description of incompatibility with magnesium stearate and possible solutions. Mol Pharm. 2017;14:3927–34.
Jonat S, Hasenzahl S, Gray A, Schmidt PC. Mechanism of glidants: investigation of the effect of different colloidal silicon dioxide types on powder flow by atomic force and scanning electron microscopy. J Pharm Sci. 2004;93:2635–44.
Ghaderi F, Nemati M, Siahi-Shadbad MR, Valizadeh H, Monajjemzadeh F. Physicochemical evaluation and non-isothermal kinetic study of the drug–excipient interaction between doxepin and lactose. Powder Technol. 2015;286:845–55.
Samanidou VF, Evaggelopoulou EN, Papadoyannis IN. Simultaneous determination of quinine and chloroquine anti-malarial agents in pharmaceuticals and biological fluids by HPLC and fluorescence detection. J Pharm Biomed Anal. 2005;38:21–8.
Brazil, Ministério da Saúde Agência - Nacional de Vigilância Sanitária. Resolução nº 166: dispõe sobre a validação de métodos analíticos e dá outras providências. 2017. http://portal.anvisa.gov.br/documents/10181/2721567/RDC_166_2017_COMP.pdf/d5fb92b3-6c6b-4130-8670-4e3263763401 Accessed 17 Oct 2017.
Hydroxychloroquine sulfate/Official Monographs. USP40-NF35. Rockville: United States Pharmacopeial Convention, Inc.; 2017. p. 4534.
Barboza F, Vecchia DD, Tagliari MP, Silva MAS, Stulzer HK. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations. Pharm Chem J. 2009;43:363–8.
Hegde DA, Hegde DD, Nagarsenker MS, Tipnis HP. Application of differential scanning calorimetry (DSC) to preformulation compatibility studies between chloroquine phosphate and tablet excipients. Indian J Pharm Sci. 1996;58:71–6.
Bertol CD, Cruz AP, Stulzer HK, Murakami FS, Silva MAS. Thermal decomposition kinetics and compatibility studies of primaquine under isothermal and non-isothermal conditions. J Therm Anal Calorim. 2010;102:187–92.
Júlio TA, Zâmara IF, Garcia JS, Trevisan MG. Compatibility of sildenafil citrate and pharmaceutical excipients by thermal analysis and LC–UV. J Therm Anal Calorim. 2013;111:2037–44.
Ledeti I, Budiul M, Matusz P, Vlase G, Circioban D, Dehelean C, Suta L-M, Caunii A, Ledeti A, Vlase T, Murariu M, Bolintineanu S. Preformulation studies for nortriptyline: solid-state compatibility with pharmaceutical excipients. J Therm Anal Calorim. 2018;131:191–9.
Peres-Filho MJ, Gaeti MPN, de Oliveira SR, Marreto RN, Lima EM. Thermoanalytical investigation of olanzapine compatibility with excipients used in solid oral dosage forms. J Therm Anal Calorim. 2011;104:255–60.
Tita B, Fulias A, Bandur G, Marian E, Tita D. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms. J Pharm Biomed Anal. 2011;56:221–7.
de Oliveira GGG, Feitosa A, Loureiro K, Fernandes AR, Souto EB, Severino P. Compatibility study of paracetamol, chlorpheniramine maleate and phenylephrine hydrochloride in physical mixtures. Saudi Pharm J. 2017;25:99–103.
Il’ves VG, Zuev MG, Sokovnin SY. Properties of silicon dioxide amorphous nanopowder produced by pulsed electron beam evaporation. J Nanotechnol. 2015;18:1–8.
Stulzer HK, Tagliari MP, Cruz AP, Silva MAS, Laranjeira MCM. Compatibility studies between piroxicam and pharmaceutical excipients used in solid dosage forms. Pharm Chem J. 2008;42:215–9.
Liltorp K, Larsen TG, Willumsen B, Holm R. Solid state compatibility studies with tablet excipients using non thermal methods. J Pharm Biomed Anal. 2011;55:424–8.
Mubtasim N, Kabir ER, Podder AK, Bhadra S. A pragmatic approach to the analysis of a combination formulation. Saudi Pharm J. 2016;24:689–97.
Daniel JSP, Veronez IP, Rodrigues LL, Trevisan MG, Garcia JS. Risperidone—solid-state characterization and pharmaceutical compatibility using thermal and non-thermal techniques. Thermochim Acta. 2013;568:148–55.
Pereira RN, Valente BR, Cruz AP, Foppa T, Murakami FS, Silva MAS. Thermoanalytical study of atenolol and commercial tablets. Lat Am J Pharm. 2007;26:382–6.
Rus LM, Tomuta I, Iuga C, Maier C, Kacso I, Borodi G, Bratu I, Bojita M. Compatibility studies of indapamide/pharmaceutical excipients used in tablet preformulation. Farmacia. 2012;60:92–101.
Gao R, Jin Y, Yang Q-Y, Sun B-W, Lin J. Study of stability and drug-excipient compatibility of estradiol and pharmaceutical excipients. J Therm Anal Calorim. 2015;120:839–45.
Li J, Wu Y. Lubricants in pharmaceutical solid dosage forms. Lubricants. 2014;2:21–43.
Acknowledgements
This work was financially supported by the following Brazilian research funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Pesquisas (FINEP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Financing code 001), Fundação de Apoio à Pesquisa da Universidade Federal de Goiás (FUNAPE) and Laboratório Central de Saúde Pública (LACEN-GO).
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Moraes, A.N.F., Silva, L.A.D., de Oliveira, M.A. et al. Compatibility study of hydroxychloroquine sulfate with pharmaceutical excipients using thermal and nonthermal techniques for the development of hard capsules. J Therm Anal Calorim 140, 2283–2292 (2020). https://doi.org/10.1007/s10973-019-08953-8
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DOI: https://doi.org/10.1007/s10973-019-08953-8