Dissolution test for oral suspension: an overview about use and importance

Soares, Thaís dos Santos Paulino; Souza, Jacqueline de; Rosa, Lorena de Sousa; Marques-Marinho, Flávia Dias

doi:10.1590/s2175-97902022e19423

Thaís dos Santos Paulino Soares

Department of Pharmacy, School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil

Jacqueline de Souza

Department of Pharmacy, School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil

http://orcid.org/0000-0003-0869-023X

Lorena de Sousa Rosa

Department of Pharmacy, School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil

Flávia Dias Marques-Marinho ^**Correspondence: F. D. Marques-Marinho. Departamento de Farmácia. Escola de Farmácia. Universidade Federal de Ouro Preto. Campus Morro do Cruzeiro, s/n, Bauxita. 35400-000, Ouro Preto, MG, Brazil. Phone/fax: +55 31 3559 1926/1069. E-mail flaviadmar@ufop.edu.br. ORCID: 0000-0002-1121-5205. Jacqueline de Souza ORCID: 0000-0003-0869-023X

Department of Pharmacy, School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil

http://orcid.org/0000-0002-1121-5205

*Correspondence: F. D. Marques-Marinho. Departamento de Farmácia. Escola de Farmácia. Universidade Federal de Ouro Preto. Campus Morro do Cruzeiro, s/n, Bauxita. 35400-000, Ouro Preto, MG, Brazil. Phone/fax: +55 31 3559 1926/1069. E-mail flaviadmar@ufop.edu.br. ORCID: 0000-0002-1121-5205. Jacqueline de Souza ORCID: 0000-0003-0869-023X

Drugs	Dissolution test conditions	Pharmacopeia
Acetazolamide(suspension)	0.01M hydrochloric acid^a; 0.9L^b; paddle^c; 50rpm^d; one dose volume^f	BP 2017British Pharmacopoeia. BP. 2018. London: Stationery Office (Great Britain) ; 2017., 2013British Pharmacopoeia. BP. 2014. London: Stationery Office (Great Britain); 2013. 5860p.
Allopurinol(suspension)	0.01M hydrochloric acid^a; 0.9L^b; paddle^c; 75rpm^d; one dose volume^f	BP 2017British Pharmacopoeia. BP. 2018. London: Stationery Office (Great Britain) ; 2017., 2013British Pharmacopoeia. BP. 2014. London: Stationery Office (Great Britain); 2013. 5860p.
Azathioprine(suspension)	water^a; 0.9L^b; paddle^c; 50rpm^d; one dose volume^f	BP 2017British Pharmacopoeia. BP. 2018. London: Stationery Office (Great Britain) ; 2017., 2013British Pharmacopoeia. BP. 2014. London: Stationery Office (Great Britain); 2013. 5860p.
Cefadroxil(for suspension)	water^a; 0.9L^b; paddle^c; 25rpm^d; 30min^e; 5mL^f; NS^g;NS^h; UV spectrophotometry at 263nmi	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013.
Cefdinir(for suspension)	0.05M phosphate buffer pH6.8^a; 0.9L^b; paddle^c; 50rpm^d; 30min^e; 5mL^f; UV spectrophotometry at 290nm^g, NS^h; NSⁱ.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013.
Cefuroxime axetil(for suspension)	0.07M phosphate buffer pH7.0^a; 0.9L^b; paddle^c; 50rpm^d; 30min^e;5mL^f; NS^g; NS^h; UV spectrophotometry at 280nmⁱ.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013.
Cefuroxime axetil(for suspension)	1.43% hydrogen ortophosphate and 0.42% sodium dihydrogen ortophosphate in water; pH 7.0 (adjust 20%v/v ortophosphoric acid or 1M sodium hydroxide)^a; 0.9L^b; paddle^c; 50rpm^d	BP 2017British Pharmacopoeia. BP. 2018. London: Stationery Office (Great Britain) ; 2017., 2013British Pharmacopoeia. BP. 2014. London: Stationery Office (Great Britain); 2013. 5860p.
Cephalexin(tablets for)	water^a, 0.9L^b, basket^c, 100rpm^d, 30min^e, UV 262nmⁱ	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018.
Ciprofloxacin (for suspension)	sodium acetate in water (6.8g/L), pH4.5 (adjust glacial acetic acid) and polyoxyethylene lauryl ether (0.25g/L)^a; 0.9L^b; paddle^c; 100rpm^d; 30min^e; 5mL^f; bottom^g; 10mL^h; HPLC/UVⁱ at 278nm.	USP, 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018.
Doxycycline (for suspension)	0.01M hydrochloric acid^a; 0.9L^b; padlle^c; 25rpm^d; 10min^e; equivalent to 25mg^f; NS^g; NS^h; HPLC/UVⁱ at 355nm.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018.
Felbamate (suspension)	water^a; 0.9L^b; paddle^c; 50rpm^d; 15min^e; 5mL^f; NS^g; NS^h; HPLC/UVⁱ at 210nm	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013.
Fluconazole (for suspension)	water^a; 0.9L^b (40mg/mL suspension) or 0.5Lb (10mg/ mL suspension); paddle^c; 50rpm^e; 30min^e; equivalent to one dose^f; NS^g; 10mL^h; HPLC/UVⁱ 260nm	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018.
Ibuprofen (suspension)	pH7.2 phosphate buffer^a; 0.9L^b; paddle^c; 50rpm^d; 60min^e; NS^f; NS^g; NS^h; HPLC/UVⁱ at 220nm	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013., 2011United States Pharmacopeia. USP . 34th ed., Rockville: United States Pharmacopeial Convention ; 2011., 2009United States Pharmacopeia. USP . 32nd ed., Rockville: United States Pharmacopeial Convention ; 2009., 2008United States Pharmacopeia. USP . 31st ed., Rockville: United States Pharmacopeial Convention ; 2008., 2006United States Pharmacopeia. USP . 29th ed., Rockville: United States Pharmacopeial Convention ; 2006., 1996United States Pharmacopeia. USP . 24th ed., Rockville: United States Pharmacopeial Convention ; 1996.; BraP 2019
Indomethacin (suspension)	0.01M phosphate buffer, pH7.2^a; 0.9L^b; paddle^c; 50rpm^d; 20min^e; equivalent to 25mg^f; surface^g; NS^h; UV spectrophotometry at 320nmⁱ.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013., 2011United States Pharmacopeia. USP . 34th ed., Rockville: United States Pharmacopeial Convention ; 2011., 2009United States Pharmacopeia. USP . 32nd ed., Rockville: United States Pharmacopeial Convention ; 2009., 2008United States Pharmacopeia. USP . 31st ed., Rockville: United States Pharmacopeial Convention ; 2008., 2006United States Pharmacopeia. USP . 29th ed., Rockville: United States Pharmacopeial Convention ; 2006., 1996United States Pharmacopeia. USP . 24th ed., Rockville: United States Pharmacopeial Convention ; 1996., 1995United States Pharmacopeia. USP . 23rd ed., Rockville: United States Pharmacopeial Convention ; 1995.
Megestrol acetate (suspension)	0.5% sodium lauryl sulfate in water^a; 0.9L^b; paddle^c; 25rpm^d; 30min^e; equivalent to 160mg^f; surface^g; NS^h; UV spectrophotometry at 292 nmⁱ	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013., 2011United States Pharmacopeia. USP . 34th ed., Rockville: United States Pharmacopeial Convention ; 2011., 2009United States Pharmacopeia. USP . 32nd ed., Rockville: United States Pharmacopeial Convention ; 2009., 2008United States Pharmacopeia. USP . 31st ed., Rockville: United States Pharmacopeial Convention ; 2008., 2006United States Pharmacopeia. USP . 29th ed., Rockville: United States Pharmacopeial Convention ; 2006.
Meloxicam (suspension)	pH7.5 phosphate buffer^a; 0.9L^b; paddle^c: 25rpm^d; 15min^e; equivalent to 7.5mg^f; NS^g; NS^h; UV spectrophotometry at 362nmⁱ.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013., 2009United States Pharmacopeia. USP . 32nd ed., Rockville: United States Pharmacopeial Convention ; 2009., 2008United States Pharmacopeia. USP . 31st ed., Rockville: United States Pharmacopeial Convention ; 2008.
Mercaptopurine (suspension)	0.01M hydrochloric acid^a; 0.9L^b; paddle^c; 50rpm^d; one dose volume^f	BP 2017British Pharmacopoeia. BP. 2018. London: Stationery Office (Great Britain) ; 2017., 2013British Pharmacopoeia. BP. 2014. London: Stationery Office (Great Britain); 2013. 5860p.
Mycophenolate mofetil (for suspension)	0.1M hydrochloric acid^a; 0.9L^b(deaerated); paddle^c; 40rpm^d; 20min^e; 1.2mL^f; surface^g; NS^h; UV spectrophotometry at 304nmⁱ.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013., 2011United States Pharmacopeia. USP . 34th ed., Rockville: United States Pharmacopeial Convention ; 2011.
Nevirapine (suspension)	0.1M hydrochloric acid^a; 0.9L^b; paddle^c; 25rpm^d; 45min^e; equivalent to 50mg^f; 1cm below the meniscus^g; 5mL^h; HPLC/UVi at 214nm	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013., 2011United States Pharmacopeia. USP . 34th ed., Rockville: United States Pharmacopeial Convention ; 2011., 2009United States Pharmacopeia. USP . 32nd ed., Rockville: United States Pharmacopeial Convention ; 2009., 2008United States Pharmacopeia. USP . 31st ed., Rockville: United States Pharmacopeial Convention ; 2008.
Nitazoxanide (for suspension)	pH 7.5 phophate buffer with 6% cetrimonium bromide^a; 0.9L^b (bath at 25°C); padlle^c; 100rpm^d; 45min^e; NS^f; NS^g; NS^h; HPLC/UVⁱ at 240nm.	BraP 2017, 2019
Oxcarbazepine (suspension)	1% sodium lauryl sulfate in water^a; 0.89L^b; paddle^c; 75rpm^d; 30min^e; 10mL^f; bottom^g; NS^h; HPLC/UVⁱ at 310nm.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013.
Phenytoin (suspension)	0.6% tris(hydroxymethyl)aminomethane and 1% sodium lauryl sulfate in water, pH 7.5 (adjust hydrochloric acid); 0.9L^b (degassed); paddle^c; 35rpm^d; 60min^e; 5mL^f; bottom^g; 4mL^h; HPLC/UVⁱ at 240nm.	USP 2018United States Pharmacopeia. USP . 41th ed., Rockville: United States Pharmacopeial Convention ; 2018., 2013United States Pharmacopeia. USP . 36th ed., Rockville: United States Pharmacopeial Convention ; 2013., 2011United States Pharmacopeia. USP . 34th ed., Rockville: United States Pharmacopeial Convention ; 2011., 2009United States Pharmacopeia. USP . 32nd ed., Rockville: United States Pharmacopeial Convention ; 2009., 2008United States Pharmacopeia. USP . 31st ed., Rockville: United States Pharmacopeial Convention ; 2008., 2006United States Pharmacopeia. USP . 29th ed., Rockville: United States Pharmacopeial Convention ; 2006.
Phenytoin (suspension)	Borate buffer^a; 0.9L^b; paddle^c; 50rpm^d; 30min^e; 5mL^f; NS^g; NS^h; HPLC/UVⁱ at 240nm.	BraP 2000Farmacopéia Brasileira. Comissão Permanente de Revisão da Farmacopeia Brasileira . 4ª ed. São Paulo: Atheneu; 2000. 282p.
Pyrazinamide (suspension)	Water^a, 0.9L^b; paddle^c; 50rpm^d; one dose volume^f	BP 2017British Pharmacopoeia. BP. 2018. London: Stationery Office (Great Britain) ; 2017., 2013British Pharmacopoeia. BP. 2014. London: Stationery Office (Great Britain); 2013. 5860p.

Drugs (formulation)	Dissolution conditions	Reference (DOI)
Esomeprazole (sachet for suspension)	0.1M hydrochloric acida; NSb; paddlec; 100rpmd; 120mine; and then in pH 6.8 buffer in 150mine; NSf; NSg; NSh; HPLC/UVi at 302nm.	Bladh et al., 2007 (10.1016/j.clinthera.2007.03.014)
Cefadroxil (powder for suspension)	Deaerated distilled watera; 0.9Lb; paddlec; 50rpmd; 7.5,15,30,45,60mine; 5mLf; middleg; 10mLh; HPLC/UVi at 230nm.	Vidal et al., 2008 (10.14227/DT150308P29)
Nimesulide (suspension)	1% polysorbate 80 in pH 6.8 simulated enteric fluida; 1Lb; paddlec; 50rpmd; 180mine; equivalent to 100mgf; NSg; NSh; spectrophotometry UV-VIS at 396nm.	da Fonseca et al., 2009da Fonseca LB, Labastie M, Sousa VP, Volpato NM. Development and validation of a discriminative dissolution test for nimesulide suspensions. AAPS PharmSciTech. 2009;10(4):1145-52. (10.1208/s12249-009-9320-4)
Roxithromycin (tablet and powder for suspension)	(A) pH 1.2, (B) pH 4.5, (C) pH 6.8 buffersa; 1Lb; 15,30,45mine; (D) pH 1.2 buffera; 0.75Lb; 60mine; then addition 0.25Lb 0.2M Na3PO4 buffer plus 1mL 2M HCl to pH 6.8a; 75, 90,105mine. Paddlesc; 75rpmd; NSf; NSg; 10mLh; HPLC/UVi at 205nm.	Ostrowski et al., 2010 (10.2478/s11536-009-0113-7)
Clarithromycin (granules for suspension)	(A) 0.1M hydrochloric acida; 0.5Lb; 30,60,90,120minf with addition pH6.8 phosphate buffera; 0.5Lb; 10,20,30,45,60mine; (B) pH5 acetate buffera; 0.9Lb; 5,10,15,20,25,30,60,90,120, 150mine; (C) pH6.8 phosphate buffer; 0.9Lb; 5,10,15,20,25,30,60,90,120, 150,180minf; (D) pH2.2 sodium citrate buffera; 0.3Lb; 60mine; with addition 0.2Lb to pH5; 30,60,90,120mine; and addition of pH6.8 0.4Lb; 30,150,180,240,300,360mine. Paddlec; 50rpmd; mass equivalent to 5mLf; NSg; 5mLh; HPLC/UVi at 210nm.	Alkhalidi, et al., 2010 (10.3109/10837450903188493)
Cefuroxime axetil (for suspension, suspension)	0.07M phosphate buffer pH7 (3.7g monobasic sodium phosphate+5.7g anhydrous dibasic sodium phosphate) a; 0.9Lb; paddlec; 50rpmd; 30 mine; 5mLf; NSg; NSh; spectrophotometry UVi at 281nm.	Valizadeh et al., 2011 (10.5681/apb.2011.014)
Buclizine hydrochloride (suspension)	1.5% sodium lauryl sulfate in watera; 0.9Lb; paddlec; 25,50rpmd; 5,10,15,20,30,60,90, 120mine; NSf; NSg; 10mLh; HPLC/UVi at 230nm.	Kuminek et al., 2012 (10.1590/S0100-40422012000100036)
Ibuprofen (suspension)	pH 7.2, pH 6.8, pH4.5 phosphate buffers and 0.1M hydrochloric acida; 0.9Lb; paddlec; 25,50rpmd; 5,10,2 0,30,45,60,90,120,150,180mine; amount equivalent to 100mg/5mLg; NSh; spectrophotometry UVi at 221nm.	Rivera-Leyva et al., 2012 (10.4103/0250-474X.107062)
Albendazole (suspension)	0.1M hydrochloric acida, 0.9Lb; paddlec; 25,50rpmd; 2,5,10,20,30,60,90mine; 5mLf; middleg; 10mLh; spectrophotometry UVi at 310nm.	Vidal et al., 2013 (10.14227/DT200413P27)
Diclofenac potassium (suspension)	0.3% sodium lauryl sulfate in watera; 0.9Lb; paddlec; 50rpmd; 5,10,15,30,60mine; amount equivalent to 10mgf; NSg; NSh; HPLC/PDAi at 275 nm.	Rubim et al., 2014 (10.1590/ S1984-82502014000200022)
Spironolactone (pediatric suspension)	0.1% sodium lauryl sulfate in 0.1M hydrochloric acida; 1Lb; paddlec; 75rpmd; 1,2,3,4,5,6,7, 8,9,10,11,12,13,14,15,60mine; 5mLf; topg; NSh; spectrophotometry UVi at 242nm.	Bernal et al., 2014 (10.14227/DT210114P19)
Carvedilol (micro/nano suspension)	pH 1 and pH 6.8 buffer mediaa; 0.9Lb; paddlec; 100rpmd; 5,15,30,60 mine; equivalent to 25mgf NSf; NSg; 5mLh; spectrophotometry UVi at 242nm.	Liu et al., 2015 (10.2147/IJN.S87143)
Montelukast sodium (suspension)	0.5% sodium lauryl sulfate in watera; 0.9Lb; paddlec; 50rpmd; 5,10,15,30mine; 4mgf; NSg; 1mLh; HPLC/UVi at 238nm.	Kim et al., 2016 (10.1007/s12272-015-0664-x)
Benzoyl metronidazole (suspension)	pH 1.2 simulated gastrintestinal fluid without enzymesa; 0.9Lb; paddlec; 50rpmd; 5,10,15,30, 45,60,90 mine; weight equivalent to 200mg/5mLf; NSg; 10mLh; HPLC/UVi at 235nm.	da Silva et al., 2016 (10.1208/s12249-015-0407-9)
Rosuvastatin (suspension)	0.05M sodium citrate buffer pH 6.6a; 0.9Lb; paddlec; 50rpmd; 10,20,30,45mine; 5mLf; in paddleg; 10mLh; HPLC/UVi at 248nm.	Zaid et al., 2017 (10.2146/ajhp160235)
Celecoxib (dry/nano suspensions)	0.1% polysorbate 80 in pH 1.2 gastric and in pH 6.8 intestinal fluidsa; 0.9Lb; paddlec; 50rpmd; 5,10,15,30,60,90,120mine; amount equivalent to 2.5mgf; NSg; 3mLh; HPLC/UVi at 250nm.	Kim et al., 2018 (10.3390/pharma ceutics10030140)
Dasatinib (powder for suspension)	0.1M hydrochloric acid pH 1.2a; 0.05Lb; 20mine (stage 1); with addition fasted state simulated intestinal fluid (FaSSIF)a; 0.25Lb; paddlec; 75rpmd; 180mine (stage 2); NSf; NSg; NSh; NSi.	Vaidhyanathan et al., 2019 (10.1016/j.xphs.2018.11.005)

Drug(s)	Reference	Generic	Interchangeable Similar	Dissolution Test Available
Cefaclor	-	4	-	No
Cefadroxil/Cefadroxil hemihydrate¹	2	6	5	Table I, II, V
Cefuroxime axetil^a	1	2	-	Table I, II, V
Cephalexin^1,2	3	12	6	Table I, V
Clarithromycin¹	2	1	2	Table II, V
Cloperastine fendizoate	1	-	-	No
Deferasirox²	-	1	-	Table V
Diclofenac acid	1	-	1	No
Diclofenac potassium	-	1	-	Table II
Diclofenac resinate	1	9	5	No
Domperidone	1	2	1	No
Erythromycin estolate	-	1	2	No
Fexofenadine hydrochloride	1	-	-	Table V
Fosamprenavir calcium	1	-	-	Table V
Ibuprofen	3	18	-	Table I, II, V
Lamotrigine²	-	2	-	No
Linezolid	-	1	-	Table V
Mebendazole	1	12	-	No
Metronidazole	-	-	3	No
Nimesulide	2	12	8	Table II
Nystatin	1	8	6	Table V
Nitazoxanide¹	1	1	5	Table I, V
Oseltamivir phosphate¹	1	-	-	Table V
Oxamniquina	1	-	-	No
Oxcarbazepine	1	2	2	Table I, V
Rifampicin¹	1	-	1	No
Secnidazole¹	-	3	-	No
Strontium ranelate¹	1	1	-	No
Sulfamethoxazole; Trimethoprim	-	4	9	Table V
Sultamicillin¹	1	-	-	No

Drug(s)^Formulation	NDA	ANDA	Dissolution Test Available
Acyclovir¹	1	2	Table V
Amoxicillin²	-	25	Table V
Amoxicillin; clavulanate potassium²	2	16	Table V
Amphetamin³	2	-	No
Ampicillin/Ampicillin trihydrate²	-	2	Table V
Aprepitant²	1	-	Table V
Atovaquone¹	1	5	No
Azithromycin²	3	14	Table V*
Barium sulfate¹	9	-	No
Bosentan⁴	1	-	Table V
Carbamazepine¹	1	2	Table V
Carbinoxamine maleate³	1	-	Table V
Cefaclor²	-	4	No
Cefadroxil/Cefadroxil hemihydrate²	-	8	Table I, II, III
Cefdinir²	-	10	Table I, V
Cefixime²	1	9	Table V
Cefpodoxime proxetil²	-	4	Table V
Cefprozil²	-	12	Table V
Cephalexin²	-	10	Table V
Chlorothiazide¹	1	-	No
Chlorpheniramine maleate; Ibuprofen; Pseudoephedrine hydrochloride¹	1	-	No
Chlorpheniramine polistirex; Codeine polistirex³	1	-	Table V
Chlorpheniramine polistirex; Hydrocodone polistirex³	-	2	Table V
Ciprofloxacin²	2	2	Table I, V*
Clarithromycin²	-	2	Table II, V*
Clobazam¹	1	6	Table V
Clozapine¹	1	-	Table V
Colesevelam hydrochloride²	2	2	No
Darunavir ethanolate¹	1	-	Table V
Deferasirox⁴	3	3	Table V
Deflazacort¹	1	-	No
Dextromethorphan polistirex³	1	2	Table V
Diazoxide¹	1	-	No
Doxycycline²	1	2	Table I, V*
Doxycycline calcium¹	1	-	No
Eltrombopag olamine²	2	-	Table V*
Esomeprazole magnesium⁵	5	-	Table V
Everolimus⁴	3	-	No
Famotidine²	1	4	Table V*
Felbamate¹	1	2	Table I, V
Fexofenadine hydrochloride¹	1	2	Table V
Fluconazole²	2	6	Table I, V*
Fosamprenavir calcium¹	1	-	Table V
Griseofulvin, microsize¹	-	4	Table V
Ibuprofen¹	6	15	Table I, II, V
Ibuprofen; Pseudoephedrine hydrochloride¹	2	1	Table V
Indomethacin¹	1	-	Table I
Levetiracetam⁴	4	-	Table V
Linezolid²	1	1	Table V*
Loperamide hydrochloride¹	1	1	Table V
Loratadine¹	1	-	No
Megestrol acetate¹	1	7	Table I
Mercaptopurine¹	1	-	Table I
Methadone hydrochloride⁴	1	3	No
Methylphenidate hydrochloride⁶	1	1	Table V
Mycophenolate mofetil¹	1	1	Table I*, V
Naproxen¹	1	1	No
Nevirapine¹	1	2	Table I, V
Nitazoxanide²	1	-	Table I, V*
Nitisinone¹	1	-	Table V
Nitrofurantoin¹	1	4	Table V
Nystatin¹	-	8	Table V
Omeprazole magnesium⁵	2	-	Table V
Omeprazole; Sodium bicarbonate²	3	4	Table V
Oseltamivir phosphate²	1	4	Table V
Oxcarbazepine¹	1	3	Table I, V
Pantoprazole sodium⁵	1	-	Table V
Paroxetine hydrochloride¹	1	-	Table V
Perampanel¹	1	-	Table V
Phenytoin¹	1	4	Table I, V
Posaconazole¹	1	-	Table V
Riluzole¹	1	-	No
Rufinamide¹	1	-	Table V
Sevelamer carbonate²	2	4	No
Sildenafil citrate²	1	-	Table V*
Simvastatin¹	2	-	Table V
Sodium polystyrene sulfonate¹	-	4	No
Sodium zirconium cyclosilicate²	2	-	No
Spironolactone¹	1	-	Table II
Stiripentol²	2	-	No
Sucralfate¹	1	-	Table V
Sulfamethoxazol; Trimethoprim¹	1	3	Table V
Tacrolimus²	2	-	No

Drug(s)^Formulation	Dissolution media	Volume	Paddle	Time
Drug(s)^Formulation	Dissolution media	(L)	(rpm)	(min^a, hour^b)
Acyclovir¹	0.1M hydrochloric acid	0.9	50	10,20,30,45,60^a
Amoxicillin² (Amox)	water (degassed)	0.9	50	5,10,15,20,30,45^a
Amox/clavulanate potassium¹	water (deaerated)	0.9	75	5,10,15,30^a
Ampicillin² (trihydrate)	water (deaerated)	0.9	25	5,10,15,20^a
Aprepitant²	1.2% polysorbate 80 in water	0.9	50	5,10,15,20a
Azithromycin³	pH 6.0 phosphate buffer	0.9	50	15,30,45,60,120,180^a
Azithromycin¹	pH 6.0 phosphate buffer	0.9	50	10,20,30,45^a
Bosentan⁴	0.5% sodium lauryl sulfate in 0.1M hydrochloric acid, pH 1.1	0.9	75	5,10,15,20,30^a
Carbamazepine¹	water (deaerated)	0.9	50	10,20,30,45,60^a
Carbinoxamine maleate³	0.4M phosphate buffer	0.895	50	0.5,1,2,3,4,6,8,12^b
Cefadroxil¹	water	0.9	25	5,10,15,30,45^a
Cefdinir¹	0.05M phosphate buffer, pH 6.8	0.9	50	10,20,30,45^a
Cefixime¹	0.05M phosphate buffer, pH 7.2	0.9	50	10,20,30,45^a
Cefpodoxime proxetil¹	0.04M glycine buffer, pH 3.0	0.9	50	10,20,30,45^a
Cefprozil²	water	0.9	25	5,10,15,20,30^a
Cefprozil monohydrate¹	water	0.9	25	5,10,15,30^a
Cephalexin¹	water	0.9	25	5,10,20,30^a
Chlorpheniramine polistirex/ Codeine polistirex³	0.1M hydrochloric acid (stage 1) pH 6.8 phosphate buffer (addition of 0.4L of 0.2M NaH2P04 to pH 6.8)	0.5	50	1^b
Chlorpheniramine polistirex/ Codeine polistirex³		0.9	50	1,2,4,6,8,12^b
Chlorpheniramine polistirex/ Hydrocodone polistirex³	Simulated gastric fluid	0.495	50	1,2,3,6,8,12,16,24^b
Ciprofloxacin¹	0.025% polyoxyethylene lauryl ether in 0.05M acetate buffer, pH 4.5	0.9	100	10,20,30,45^a
Clarithromycin¹	0.05M phosphate buffer, pH 6.8	0.9	50	10,20,30,45,60^a
Clobazam¹	0.1M hydrochloric acid (degassed)	0.9	75	5,10,15,20,25,30^a
Clozapine¹	pH 4.0 acetate buffer	0.9	50	5,10,15,20,30^a
Darunavir ethanolate¹	0.05% polysorbate 20 in 0.05M phosphate buffer, pH 6.8	0.9	75	5,10,15,20,30,45^a
Deferasirox⁴	0.5% polysorbate 20 in phosphate buffer, pH 6.8	0.9	50	10,20,30,45^a
Dextromethorphan polistirex³	0.1M hydrochloric acid	0.5	50	30,60,90,180^a
Doxycycline¹	0.01M hydrochloric acid	0.9	25	5,10,15,20^a
Eltrombopag olamine¹	50 mM potassium phosphate in water, pH 6.8 with 0.2% polysorbate 80	0.75	50	4,8,12,15,20^a
Erythromycin ethylsuccinate¹	1% sodium lauryl sulfate in monobasic sodium phosphate buffer, pH 6.8	0.9	75	10,20,30,45,60^a
Esomeprazole magnesium⁵	0.1M hydrochloric acid (stage 1) pH 6.8 sodium phosphate buffer (stage 2)	0.3	100	120^a
Esomeprazole magnesium⁵		1.0	100	10,20,30,45,60^a
Famotidine¹	0.1M phosphate buffer, pH 4.5	0.9	25, 50	10,15,30,45^a
Felbamate¹	water (deaerated)	0.9	50	5,10,15,30^a
Fexofenadine hydrochloride¹	0.001M hydrochloric acid	0.9	50	10,20,30,45^a
Fluconazole¹ (40mg/mL) (10mg/mL)	water (deaerated)	0.9	50	10,20,30,45^a
Fluconazole¹ (40mg/mL) (10mg/mL)	water (deaerated)	0.5	50	10,20,30,45^a
Fosamprenavir calcium¹	10mM hydrochloric acid	0.9	25	5,10,15,20^a
Griseofulvin¹ (microsize or not)	0.54% sodium lauryl sulfate in water	1.0	25, 50	10,20,30,45^a
Ibuprofen⁶	pH 7.2 phosphate buffer	0.9	50	5,10,15,20^a
Ibuprofen/ pseudoephedrine hydrochloride¹	0.05M phosphate buffer, pH 7.2	0.9	50	5,10,15,30^a
Levetiracetam⁴	pH 6.8 phosphate buffer (degassed)	0.9	50	2.5,5,10,15,20^a
Linezolid¹	0.05M phosphate buffer, pH 6.8	0.9	50	10,20,30,45^a
Loperamide hydrochloride¹	0.01M hydrochloric acid	0.9	25	10,20,30,45,60,75,90^a
Meloxicam¹	pH 7.5 phosphate buffer	0.9	25	5,10,15,30^a
Mercaptopurine¹	0.1M hydrochloric acid	0.9	50	5,10,15,20,30^a
Methylphenidate hydrochloride⁷	0.4M phosphate buffer, pH 4.5	0.9	75	0.25,0.5,1,2,3,4,6,8^b
Mycophenolate mofetil¹	0.1M hydrochloric acid	0.9	40	5,10,20,30^a
Nevirapine¹	0.1M hydrochloric acid	0.9	25	10,20,30,45,60^a
Nitazoxanide¹	6% hexadecyltrimethyl ammonium bromide in phosphate buffer, pH 7.5	0.9	100	10,20,30,45,60^a
Nitisinone¹	pH 1.2 hydrochloric acid buffer (degassed)	1.0	50	10,15,20,30,45^a
Nitrofurantoin¹	pH 7.2 phosphate buffer	0.9	50	15,30,60,120,180^a
Nystatin1	0.1% and 0.2% sodium lauryl sulfate in water	0.9	25,50,75	5,10,20,30,45,60^a
Omeprazole sodium bicarbonate²	0.25 mM sodium phosphate buffer, pH 7.4	0.9	50	5,10,15,30^a
Oseltamivir phosphate¹	0.1M hydrochloric acid	0.9	25	5,10,15,20,30^a
Oxcarbazepine¹	1% sodium lauryl sulfate in water	0.9	75	10,20,30,45^a
Pantoprazole sodium⁸	0.1M hydrochloric acid (stage 1) 0.05M tribasic sodium phosphate/TSP pH 6.8 (add 0.25L of 0.2mM TSP)	0.75	100	60,90,120^a
Pantoprazole sodium⁸		1.0	100	10,20,30,45,60^a
Paroxetine hydrochloride¹	Simulated gastric fluid without enzyme	0.9	100	10,20,30,45^a
Perampanel¹	0.1M hydrochloric acid	0.89	50	5,10,15,20,30^a
Posaconazole¹	0.3% sodium lauryl sulfate	0.9	25	10,20,30,45^a
Rufinamide	2.0% sodium lauryl sulfate in water	0.9	50	5,10 15,20,30^a
Sildenafil citrate¹	McIlvaine buffer, pH 5.0	0.5	50	5,10,15,20,30^a
Simvastatin¹	0.14% sodium lauryl sulfate in phosphate buffer, pH 7.0	0.9	50	10,15,20,30,45^a
Sucralfate¹	0.1M hydrochloric acid/0.067 M potassium chloride, pH 1.0	0.9	75	10,20,30,45^a
Sulfamethoxazole/ trimethoprim¹	1mL of 0.2M hydrochloric acid in water	0.9	50	10,20,30,45,60,90^a
Voriconazole¹	0.1M hydrochloric acid	0.9	50	10,20,30,45^a

BCS	Drug^(Reference)	Reference^(DOI)
I	Chlorpheniramine^20,43	1 - Almukainzi et al., 2015 ^{(10.1208/s12249-014-0241-5)}
	Hydrocodone²⁸	2 - Alvarez et al., 2011 ^{(10.1002/jps.22472)}
	Oseltamivir^41,45	3 - Bajaj et al., 2012 ^{(10.3109/03639045.2012.683440)}
	Paroxetine hydrochloride⁴¹	4 - Bialer, Midha, 2010 ^{(10.1111/j.1528-1167.2010.02573.x)}
	Sildenafil citrate^20,41,43,47	5 - Breda et al., 2009 ^{(10.1016/j.ijpharm.2008.12.026)}
II	Azithromycin^20,41,43	6 - Campos et al., 2007 ^{(10.1055/s-0031-1296624)}
	Bosentan^25,54	7 - Charoo et al., 2014 ^{(10.1002/jps.2418)}
	Carbamazepine^{4,20,33,39,47,50,52,54}	8 - Chilukuri et al., 2014^{(10.1093/chromsci/bmt110)}
	Carvedilol^41,43,47	9 - Cho et al., 2012 ^{(10.1007/s40005-012-0020-9)}
	Celecoxib^20,21	10 - Choonara et al., 2014 ^{(10.1208/s12249-014-0271-z)}
	Clarithromycin^35,41	11 - Chuasuwan et al., 2009 ^{(10.1002/jps.21525)}
	Clozapine^16,61	12 - Corrêa et al., 2014 ^{(10.1080/10408347.2013.826573)}
	Darunavir ethanolate¹²	13 - Cristofoletti et al., 2016 ^{(10.1016/j.xphs.2015.11.033)}
	Dasatinib⁵⁵	14 - da Fonseca et al., 2009da Fonseca LB, Labastie M, Sousa VP, Volpato NM. Development and validation of a discriminative dissolution test for nimesulide suspensions. AAPS PharmSciTech. 2009;10(4):1145-52.^{(10.1208/s12249-009-9320-4)}
	Deferasirox¹⁸	15 - da Silva et al., 2015 ^{(10.1208/s12249-015-0407-9)}
	Diclofenac potassium¹¹	16 - Dias et al., 2014 ^{(10.1007/s10973-014-4142-3)}
	Felbamate^4,20	17 - Douroumis, Fahr, 2007 ^{(10.1016/j.colsurfb.2007.05.009)}
	Fosamprenavir calcium^8,54	18 - Durdunji et al.,2016 ^{(10.1016/j.ejpb.2016.02.006)}
	Ibuprofen^{2,20,33,38,43,46,47,50,52,14}	19 - Fairstein et al., 2013 ^{(10.1208/s12248-013-9462-x)}
	Indomethacin^20,40	20 - FDA, NICHD ^{(bpca.nichd.nih.gov/collaborativeefforts/initiatives/documents/formulations_platform_report1.pdf)}
	Loperamide HCl^56,59	21 - Fong et al., 2015 ^{(10.1016/j.ijpharm.2015.10.029)}
	Megestrol acetate^26,36	22 - Fujioka et al., 2007 ^{(10.1016/j.jconrel.2007.03.002}
	Meloxicam^8,9,41,43	23 - Fujioka et al., 2008 ^{(10.1016/j.ijpharm.2007.10.008)}
	Methylphenidate HCl²⁰	24 - Ghadi, Dand, 2017 ^{(10.1016/j.jconrel.2017.01.014)}
	Mycophenolate mofetil^20,47,49	25 - Ghasemian et al., 2016 ^{(10.15171/apb.2016.029)}
	Nevirapine^20,33,51	26 - Guk et al., 2017 ^{(10.1111/bcpt.12677)}
	Nimesulide¹⁴	27 - Helmy, Bedaiwy, 2016 ^{(10.14227/DT230316P32)}
	Phenytoin^{33,38,43,50,52}	28 - Hemmingsen et. al., 2011 ^{(10.3390/pharmaceutics3010073)}
	Posaconazole^13,29	29 - Hens et al., 2016 ^{(10.1002/jps.24690)}
	Rufinamide⁴	30 - Israr et al., 2014 ^{(10.1590/S1984-82502014000400030)}
	Simvastatin^20,41,47,50	31 - Jha et al., 2014 ^{(10.1155/2014/452051)}
III	Ampicillin⁴⁹	32 - Kalvakuntla et al., 2016 ^{(10.15171/apb.2016.013)}
	Cefadroxil²⁰	33 - Kasim et al., 2004 ^{(10.1021/mp034006h)}
	Cefprozil²⁰	34 - Khan et al., 2010 ^{(10.1208/s12249-010-9505-x)}
	Clavulanate potassium^20,54	35 - Kristin et al., 2017 ^{(10.1016/j.ejps.2017.02.003)}
	Codeine^{20,33,38,43,47}	36 - Li et al., 2015 ^{(10.1007/s12272-015-0604-9)}
	Esomeprazole magnesium^20,54	37 - Liew et al., 2014 ^{(10.3109/03639045.2013.798805}
	Pantoprazole sodium^6,20,54	38 - Lindenberg et al., 2004 ^{(10.1016/j.ejpb.2004.03.001)}
	Rosuvastatin^20,54	39 - Mishra et al., 2010Mishra V, Gupta U, Jain N. Biowaiver: an alternative to in vivo pharmacokinetic bioequivalence studies. Pharmazie. 2010;65(3):155-61.^{(10.1691/ph.2010.9231)}
IV	Acetazolamide^20,24,33,38	40 - Nokhodchi et al., 2005 ^{(sites.ualberta. ca/~csps/JPPS8(1)/ A.Nokhodchi/indomethacin.pdf)}
	Aprepitant^24,32	41 - Ono et al., 2016 ^{(10.5599/admet.4.4.338)}
	Azathioprine^{20,24,33,38,50}	42 - Pál et al., 2013 ^{(10.1016/j.ejps.2013.03.006)}
	Benzoyl metronidazole^15,50	43 - Papich, Martinez, 2015 ^{(10.1208/s12248-015-9743-7)}
	Cefdinir^20,41,53,54	44 - Petrusevska et al., 2015 ^{(10.1002/jps.24350)}
	Cefixime^20,47	45 - Ploger et al., 2018 ^{(10.1016/j.xphs.2018.01.025)}
Two or more	Acyclovir: III^{20,33,38,39,50}, IV^20,41
	Albendazole: II^{33,38,50,52,57}, IV³⁸
	Allopurinol: I^20,54, II⁴¹, III2^0,38,54, IV^33,50
	Amoxicillin: III^33,43,52, IV^47,50,52
	Cefpodoxime proxetil: II³⁴, IV³	46 - Potthast et al., 2005 ^{(10.1002/jps.20444)}
	Cefuroxime axetil: II³⁰, IV^20,47,54	47 - Ramirez et al., 2010 ^{(10.1111/j.1365-2125.2010.03757.x)}
	Cephalexin: III^37,52, IV^20,43,52	48 - Resende et al., 2016 ^{(10.1590/s1984-82502016000400005)}
	Ciprofloxacin: II³⁸, III^20,33,50,52,IV^5,38,43	49 - Rumondor et al., 2016 ^{(10.1016/j.xphs.2015.11.004)}
	Doxycycline: I^38,43, III⁵², IV^33,43,50,52	50 - Santos et al., 2014 ^{(10.1590/S1984-82502011000100002)}
	Famotidine: III^20,41,31, IV^24,47	51 - Sarkar et al., 2008 ^{(10.4103/0250-474X.45401)}
	Fexofenadine HCl: I^20,41 , III^9,20	52 - Shawahna, 2016 ^{(10.1208/s12248-016-9885-2)}
	Fluconazole: I^20,38, II⁴¹, III^{20,27,33,47,50}	53 - Thota et al., 2014 ^{(IJPSN-3-20-14-KISHAN)}
	Griseofulvin: II^{20,22,23,33,38,39,54}, IV^20,33,54	54 - Tiwari et al., 2014 ^{(10.7897/2277-4572.035187)}
	Levetiracetam: I^43,44, III^20,47	55 - Vaidhyanathan et al., 2019 ^{(10.1016/j.xphs.2018.11.005)}
	Linezolid: I^27,43, IV^20,43,54	56 - Venkateswarlu et al., 2016 ^{(10.15171/apb.2016.050)}
	Mercaptopurine: II^58,60, IV²⁰	57 - Vidal et al., 2014 ^{(10.14227/DT210214P42)}
	Montelukast sodium: I^20,41,54, II¹	58 - Wang et al., 2015 ^{(10.1016/j.bmcl.2015.01.022)}
	Nitrofurantoin: II³⁸, IV^33,52	59 - Widjojokusumo et al., 2013 ^{(10.1007/s11814-013-0115-7)}
	Nystatin: III^20,33,38, IV^38,42	60 - Yang et al., 2016 ^{(10.1248/cpb.c15-00949)}
	Oxcarbazepine: II^4,17, IV^20,47	61 - Zeng et al., 2013 ^{(10.1208/s12249-013-9973-x)}
	Pseudoephedrine HCl: ^I41 , IV⁴¹
	Pyrazinamide: I^38,20, III^33,20,47
	Spironolactone: II^33,38,48, IV³⁸
	Sulfamethoxazole: II^10,20,38, IV^20,33,50,52
	Trimethoprim: II³⁸, IV^20,33,50,52

Drug	Dissolution media	Drug solubility mg.mL^{-1 (Ref.; DOI)}	Oral suspension drug concentration (mg.mL^-1)	Drug concentration in 0.9L dissolution media (mg.mL^-1)	Pharmacological maximum single dose (mg)	*Minimum mL for sink* condition**
Acetazolamide	0.01M hydrochloric acid	1.23 ^{(Granero et al., 2008; 10.1002/jps.21282)}	25	0.28	250	610^a
Albendazole	0.1M hydrochloric acid	0.900^{(Vidal et al., 2013; *)}	40	0.22	400	667^b
Azathioprine	water	0.130^{(Newton et al.., 1982; doi. org/ 10.1016/0378-5173(82)90039-4)}	10; 50^b	0.011; 0.055	150	1,153^b
Benzoyl metronidazole	pH1.2 simulated gastric fluid without enzymes	0.66 ^{(da SILVA et al., 2016;*)}	40	0.22	200	909^a
Buclizine hydrochloride	water with 1.5% sodium lauryl sulfate	0.0825 ^{(Kuminek et al., 2012; 10.1590/S0100- 40422012000100036)}	1	0.005	25	909^a
Carvedilol	pH 1.2 buffer	0.832	25	0.028	80	289^a
Carvedilol	pH 6.8 buffer	0.0315 ^{(Hamed et al., 2015; 10.1208/s12249-015-0365-2)}	25	0.028	80	7,619^a
Cefadroxil	water	1.11^{(Drugbank;**)}	50; 100	0.28; 0.56	1000	2,702^a
Cefdinir	0.05M phosphate buffer pH6.8	0.48^{(Thota et al., 2014; IJPSN-3-20-14-KISHAN)}	25; 50	0.14; 0.28	600	3,750^a
Cephalexin	water	1.789^{(Drugbank, 2019;**)}	25; 50	0.14; 0.28	1000	419^b
Clarithromycin	pH 5 acetate buffer	14.42	25; 50	0.14; 0.28	500	104^a
Clarithromycin	pH 6.8 phosphate buffer	0.57 ^{(Morakul et al., 2014; 10.1016/ j.ejpb.2014.08.013)}	25; 50	0.14; 0.28	500	2,631^a
Diclofenac potassium	water with 0.3% sodium lauryl sulfate	0.197 ^{(Rubim et al.,2014;*)}	1.8	0.011	50	761a
Felbamate	water	0.742 ^{(Drugbank, 2006;**)}	120	0.67	600	2,426^a
Fluconazole	water	7.5 ^{(Charoo et al.,2014; 10.1002/jps .24181)}	10; 40	0.22b	800	320^a
Ibuprofen	pH 7.2 phosphate buffer	5.86	20; 50; 100; 300	0.11; 0.28; 0.56; 1.67	800	768^b
	pH 6.8 phosphate buffer	5.57	20	0.89		431^a
	pH 4.5 phosphate buffer	5.1	20	0.89		470^a
	0.1M hydrochloric acid	2.18^{(Rivera-Leyva et al., 2012;*)}	20	0.89		1,100^a
Indomethacin	pH 7.2 phosphate buffer	0.7675 ^{(Nokhodchi et al.,2005; (sites.ualberta.ca/~csps/JPPS8(1)/A. Nokhodchi/indomethacin.pdf)}	5	0.11^a	100	391^a
Nevirapine	0.1M hydrochloric acid	4.32 ^{(Sarkar et al., 2008; 10.4103/ 0250-474X.45401)}	10	0.056	200	139^b
Nimesulide	pH 6.8 simulated enteric fluid+ 1% polysorbate 80	0.1477 da Fonseca et al, 2009da Fonseca LB, Labastie M, Sousa VP, Volpato NM. Development and validation of a discriminative dissolution test for nimesulide suspensions. AAPS PharmSciTech. 2009;10(4):1145-52.^;*)	10; 50	0.22	200	4,062^a
Pyrazinamide	water	20.3^{(Becker et al., 2008; 10.1002/ jps.21250)}	10; 100	0.11	500	73.89^a
Roxithromycin	pH 4.5 acetate buffer	0.00037	10	0.055	300	405,405^b
Roxithromycin	pH 6.8 phosphate buffer	74.8x10-6^{(Liebenberg, 2011;***)}	10	0.055	300	2,005,347^b

[1] *Correspondence: F. D. Marques-Marinho. Departamento de Farmácia. Escola de Farmácia. Universidade Federal de Ouro Preto. Campus Morro do Cruzeiro, s/n, Bauxita. 35400-000, Ouro Preto, MG, Brazil. Phone/fax: +55 31 3559 1926/1069. E-mail flaviadmar@ufop.edu.br. ORCID: 0000-0002-1121-5205. Jacqueline de Souza ORCID: 0000-0003-0869-023X

Brasil

Brasil

Dissolution test for oral suspension: an overview about use and importance

Abstract