Development of an oral suspension containing dry extract of <i>Aleurites moluccanus</i> with anti-inflammatory activity

Richie Mac Donald

Programa de Pós-graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Sabrina Santana Camargo

Núcleo de Investigações Químico-Farmacêuticas, Curso de Farmácia, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Christiane Meyre-Silva

Programa de Pós-graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Núcleo de Investigações Químico-Farmacêuticas, Curso de Farmácia, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Nara Lins Meira Quintão

Programa de Pós-graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Núcleo de Investigações Químico-Farmacêuticas, Curso de Farmácia, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Valdir Cechinel Filho

Programa de Pós-graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Núcleo de Investigações Químico-Farmacêuticas, Curso de Farmácia, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Tania Mari Bellé Bresolin

Programa de Pós-graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Núcleo de Investigações Químico-Farmacêuticas, Curso de Farmácia, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Ruth Meri Lucinda-Silva ^** Corresponding author. rlucinda@univali.br

Programa de Pós-graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Núcleo de Investigações Químico-Farmacêuticas, Curso de Farmácia, Universidade do Vale do Itajaí, Itajaí, SC, Brazil

Authors contributions

RMD and SSC carried out the laboratory work, data analysis and writing of the manuscript. NLMQ supervised the pharmacological studies and contributed to critical writing and reading of the manuscript. CMS and VCF contributed to botanical, phytochemistry and analytical studies. TMBB and RMLS contributed to designed the study, supervised the analytical and technological studies and contributed to critical writing and reading of the manuscript. All the authors have read the final manuscript and approved the submission.

Batches	I	II	III	IV	V	VI	VII	VIII	IX	X
Dry extract (mg/ml)	100	100	100	100	100	100	100	100	50	50
CS ^a a CS, carmellose sodium; MCCS, microcrystalline cellulose and carmellose sodium mixture. (%)	1.0	1.0	0.5	0.5	–	–	–	–	0.5	–
MCCS ^a a CS, carmellose sodium; MCCS, microcrystalline cellulose and carmellose sodium mixture. (%)	–	–	–	–	1.0	1.0	0.5	0.5	–	1.0
Sucralose (%)	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1
Na benzoate (%)	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1
Sorbitol (%)		50	–	50	–	50	–	50	20	20
Water	qsp	qsp	qsp	qsp	qsp	qsp	qsp	qsp	qsp	qsp

Batches	pH	Rate of settling ^a a Rate of settling after 8 h. (%)	Sediment characteristic	Supernatant characteristic ^c c + cloudy; ++ less cloudy; +++ clear.	Resuspension (min)	Viscosity (mPas s)	n ^d d Index of flow behaviour.
I	5.10 ± 0.02	49.67 ± 0.03	Compact	+	0.28 ± 0.02	35.67 ± 2.13	0.74 ± 0.03
II	4.56 ± 0.02	98.00 ± 0.03	Loose	++	0.28 ± 0.02	44.28 ± 3.69	0.63 ± 0.71
III	4.77 ± 0.01	40.00 ± 0.07	Loose	+++	0.19 ± 0.01	25.83 ± 3.69	0.19 ± 0.02
IV	4.82 ± 0.02	83.66 ± 0.06	Loose	+++	0.33 ± 0.02	38.13 ± 2.13	0.98 ± 0.10
V	5.06 ± 0.01	39.66 ± 0.00	Loose	++	0.06 ± 0.01	38.13 ± 2.13	0.18 ± 0.02
VI	4.46 ± 0.00	75.66 ± 0.02	Loose	++	0.10 ± 0.02	44.28 ± 3.69	0.20 ± 0.07
VII	4.81 ± 0.00	25.66 ± 0.00	Loose	++	0.08 ± 0.01	38.13 ± 2.13	0.25 ± 0.02
VIII	4.83 ± 0.01	39.00 ± 0.06	Loose	+++	0.10 ± 0.01	18.45 ± 0.00	0.63 ± 0.02
IX	5.17 ± 0.03	nd ^b b It did not observed the sediment formation.	Compact	+	0.61 ± 0.02	53.20 ± 1.99	0.91 ± 0.08
X	5.08 ± 0.03	33.00 ± 0.04	Loose	++	0.05 ± 0.00	6.45 ± 0.18	0.24 ± 0.02

Analysis	Batches
	IX		X
	t ₀	t ₁₈₀	t ₀	t ₁₈₀
30°C (long time study)
pH	5.17 ± 0.03	5.03 ± 0.01	5.08 ± 0.03	4.93 ± 0.11
Redispersion time (s)	36.77 ± 1.26	11.33 ± 1.52	3.16 ± 0.23	2.60 ± 0.57
Viscosity (mPa s)	53.20 ± 1.99	20.5 ± 1.42	6.45 ± 0.18	3.69 ± 0.0
Zeta potential	-33.90 ± -33.90	-41 ± 4.12	-33.5 ± 5.79	-35.1 ± 5.77
TP ^a a TP: total phenolic expressed in swertisin. (mg/ml)	1.70 ± 0.04	1.40 ± 0.004	1.68 ± 0.007	1.44 ± 0.011
TP ^a a TP: total phenolic expressed in swertisin. dissolved (%)	1.58 ± 0.04	1.37 ± 0.05	1.54 ± 0.03	1.38 ± 0.004

40°C (accelerated study)
pH	5.17 ± 0.03	4.93 ± 0.02	5.08 ± 0.03	4.92 ± 0.03
Redispersion time (s)	36.77 ± 1.26	8.33 ± 2.56	3.16 ± 0.23	2.00 ± 0.50
Viscosity (mPa s)	53.20 ± 1.99	8.61 ± 1.73	6.45 ± 0.18	9.84 ± 2.13
Zeta potential	-33.90 ± -33.90	-37.7 ± 4.65	-33.5 ± 5.79	-33.3 ± 5.41
TP ^a a TP: total phenolic expressed in swertisin. (mg/ml)	1.70 ± 0.04	1.46 ± 0.02	1.68 ± 0.007	1.47 ± 0.03
TP ^a a TP: total phenolic expressed in swertisin. dissolved (%) ^b b Total phenolic dissolved in 10 min.	1.58 ± 0.04	1.37 ± 0.03	1.54 ± 0.03	1.32 ± 0.02

Recovery
Theoretical TP added (µg/ml)	Practical TP added (µg/ml)	Recovery (%)	Average (%)	% RSD
19.26	22.34	116.00	103.13	10.82
32.10	30.83	90.06
44.94	43.74	97.34
Repeatability and Intermediary precision ^a a Analysis in 6 replicates.
	Analyst 1	Analyst 2	Intermediary precision
TP expressed in swertisin (mg/ml)	1.54	1.62	1.58
RSD%	2.24	1.37	3.37

Linearity
Intercept	R		F _calc		F _crit
−41,648.99	0.9967		1510.53		2.12 × 10⁻⁰⁷
Recovery
Batches	IX				X
Theoretical TP added (µg/ml)	Practical TP added (µg/ml)			Recovery (%)	Practical TP added (µg/ml)		Recovery (%)
4.94	5.31			107.60	5.25		106.38
8.92	8.92			100.01	9.15		102.58
12.82	13.22			102.74	12.35		95.99

Average %			103.45		Average %		101.65
RSD%			3.71		RSD%		5.16
Repeatability and intermediary precision ^a a Analysis in 6 replicates.
	IX				X
	Analyst			Intermediary precision	Analyst		Intermediary precision
	1	2			1	2
TP assay (mg/ml)	1.69	1.52		1.60	1.65	1.53	1.59
DPR%	2.96	2.54		7.48	1.78	1.57	4.87

Brasil