Int J Pharm Pharm Sci, Vol 9, Issue 2, 154-159Original Article


STANDARDIZATION AND STABILITY EVALUATION OF DRY EXTRACTS OF MYRACRODRUON URUNDEUVA ALLEMÃO OBTAINED BY SPRAY DRIER

RENATA DA SILVA LEITEa*, VALMIR GOMES DE SOUZAb, AGNA HÉLIA DE OLIVEIRAb, JOSÉ VENÂNCIO CHAVES JÚNIORb, ISLAINE DE SOUZA SALVADORb, FABRICIO HAVY DANTAS DE ANDRADEb, RUI OLIVEIRA MACEDOb, FÁBIO SANTOS DE SOUZAb

aDepartamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, Brazil, bDepartamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Brazil
Email: renataleitesp@yahoo.com.br

Received: 05 Sep 2016 Revised and Accepted: 21 Dec 2016

ABSTRACT

Objective: This study aimed to obtain standardised dry extracts of Miracrodruon urundeuva Allemão using spray-dryer and evaluate the stability of the extracts.

Methods: It evaluated the drying parameters: Proportion of colloidal silicon dioxide (CSD) (10, 15 and 20%), inlet temperature (160, 170 and 180 °C) and feed rate (4, 6 and 8 ml/min). The study of the accelerated stability of dry extract occurred in temperature of 40 °C (±2 °C) and relative humidity of 75% (±5%) for 6 mo. The anti-inflammatory activity of the dry extract was evaluated in Swiss mice by the paw edema method.

Results: Variations in drying conditions did not represent significant variations in yields of the process. The drying temperature and feed rate significantly influenced the concentration of quercetin (p≤0.05). The increase in inlet temperature and feed flow promoted the increase of quercetin concentration in the extracts. The stability study showed that the concentration of quercetin in dry extract was stable over a period of 6 mo. The dry extract showed anti-inflammatory activity in mice orally.

Conclusion: A condition of 10% of colloidal silicon dioxide with an 180 °C inlet temperature and a feed rate of 8 ml/min was considered the most adequate for obtaining the extracts and the drying process resulted in stable dry extracts and the quercetin was a suitable biomarker for monitoring the process.

Keywords: Myracrodruon urundeuva Allemão, Dry extracts, Spray dryer, Stability

© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4. 0/)
DOI: http://dx.doi.org/10.22159/ijpps.2017v9i2.15065

INTRODUCTION

The Miracrodruon urundeuva Allemão is an arboreal species of the Anacardiaceae family, which is native to Brazil but also found in Mexico, Argentina, Bolivia and Paraguay, that is used in folk medicine for its medicinal properties [1]. Studies using extracts from different parts of this plant have shown anti-ulcer activity [2-4], anti-inflammatory and wound healing properties [4, 5], antibacterial and antifungal properties [6], neuroprotective qualities [7] and cytotoxicity in cancer cells [8].

The study of an ethanolic extract of leaves of M. urundeuva showed a higher incidence of secondary metabolites in the species than those derived from phenolic acids [9]. Phytochemical studies of the stem and leaf showed the presence of tannins, flavonoids, mono and sesquiterpenes, triterpenes and steroids, condensed proantho-cyanidins and leucoanthocyanidins and sugars [10, 11].

Quercetin is a flavonoid identified in M. urundeuva known to express pharmacological activity as an antioxidant, anti-inflammatory and antimicrobial, among others [12-16]. Thermoanalytical studies indicate that this compound is stable up to 315 °C when it starts the process of decomposition [17].

The development of standardised plant derivatives with defined chemical, physical, and technological characteristics is fundamental in the herbal industry and results in obtaining pharmaceutical forms with assured quality to ensure reproducibility in the preparation of a medicinal product and its therapeutic efficacy [18].

The use of dry extracts in the production of herbal medicines has been employed due to their greater chemical stability; physiochemical and microbiological characteristics; higher concentrations of active compounds; ease of patterning and handling; and greater processing capacity in different pharmaceutical formulations than liquid extracts [19, 20].

Among the techniques successfully employed in the preparation of dry plant extracts is the nebulization by spray drying, which produces powders with defined characteristics, such as shape and particle size, and the rapid evaporation of the solvent reduces the process time and risk of changes of thermolabile products [21-24].

This study aimed to obtain standardised dry extracts of Miracrodruon urundeuva Allemão using spray drying and to evaluate the stability and anti-inflammatory activity of the dry extracts obtained.

MATERIALS AND METHODS

Plant material and chemicals

This study used leaves of Myracrodruon urundeuva Allemão (Anacardeaceae) collected from farms in Cacimbas and Caraúbas in the state of Paraiba, Brazil. Entire plants were collected during the flowering stage. A representative sample of this species is deposited in the Lauro Pires Xavier Herbarium of the Federal University of Paraíba (Registration no. NC240) and botanical identification was carried out by Professor Alecksandra Vieira Lacerda of the Federal University of Campina Grande. The plant material was dried at 50+2 °C for 96 h in a circulating air oven, reduced to a powder in a mechanical mill, and stored in sealed plastic bag. The hydroethanolic extract of the plant was obtained by the maceration at 25 °C of 2 kg of powdered leaves in 10l of ethanol/water solution 50% (v/v) for 120 h.

HPLC grade solvents were purchased from Tedia Co. (Phoenix, AZ-USA). The standard employed in the analyses was quercetin dehydrate CAS–117-39-5 (97% pure) that had been acquired by Merck, Brazil. The colloidal silicon dioxide (Henrifarma, Brazil) was used as a drying agent. Carrageenan (Sigma-Aldrich, Brazil) and diclofenac sodium (Novartis, Brazil) were used in the study of the anti-inflammatory activity.

Spray-drying

The spray-drying process was performed in a laboratory-scale model SD-05 (Lab-Plant, Hudders field, UK). The atomiser double pneumatic fluid nozzle with 1.2 mm opening hole operated with an airflow rate of 62 m3/h and a 2.0 bar of pressure. A 23+1factorial experimental design was used to assess the effect of spray-drying operating variables on yield and quercetin concentration on the drier extract. Three factors at two levels were considered: (A) drying air inlet temperature (160, 170 and 180 °C), (B) the flow rate of the drying composition fed to the spray drying (4, 6 and 8 ml/min) and (C) the proportion of colloidal silicon dioxide (CSD) (10, 15 and 20%). Table 1 summarises the levels of operating variables.

The silicon dioxide was selected for the study because it is an adjuvant with a high surface area and thermal stability, it is a safe excipient when used in pharmaceuticals for oral and topical use, and it is widely used as a technological adjuvant in the drying of vegetable extracts by spray drying [25].

Table 1: Experimental matrix according to 23+1 factorial design and studied responses. T: inlet temperature, F: feed rate, CSD: proportion of colloidal silicon dioxide

Run A B C T ( °C) F (ml/min) CSD (%)
1 1 -1 1 180 4 20
2 1 1 1 180 8 20
3 1 -1 -1 180 4 10
4 -1 1 -1 160 8 10
5 -1 1 1 160 8 20
6 1 1 -1 180 8 10
7 -1 -1 -1 160 4 10
8 -1 -1 1 160 4 20
9 0 0 0 170 6 15

T: inlet temperature, F: feed rate, CSD: proportion of colloidal silicon dioxide.

Run A B C T ( °C) F (ml/min) P (%)
1 1 -1 1 180 4 20
2 1 1 1 180 8 20
3 1 -1 -1 180 4 10
4 -1 1 -1 160 8 10
5 -1 1 1 160 8 20
6 1 1 -1 180 8 10
7 -1 -1 -1 160 4 10
8 -1 -1 1 160 4 20
9 0 0 0 170 6 15

T: inlet temperature, F: feed rate, P: the proportion of CSD®.

Quercetin content

The quercetin content was quantified by High-performance liquid chromatography (HPLC) according to the method previously validated. A calibration curve relating the peak area with quercetin concentration was built using linear regression analysis. The fitted equation (y = 56948x–6354) was linear over the range of 0.4 to 7.6 µg/ml presenting a R2>0.999. Parameters of validation such as selectivity, linearity, detection and quantification limits (LOD and LOQ, respectively) and precision or relative standard deviation (RSD) were established [26, 27]. The LOD and LOQ were evaluated on the basis of the noise obtained with analysis of non-spiked blank samples for quercetin (n = 3). LOD and LOQ were defined as the concentration of the analytic that produced a signal-to-noise ratio of 3 and 10, respectively [26]. For the total quercetin, the LOD and LOQ were estimated by the slope and mean standard deviation of quercetin concentrations used in the standard curve [27]. The LOD for the quercetin was 0.18 μg/ml, while LOQ was 0.56 μg/ml. Results of six parallel experiments indicated that precision or RSD were all<5%.

HPLC analyses were conducted in a Shimadzu liquid chromate-graphy (Shimadzu, Kyoto, Japan) coupled with a photo diode array detector (PD-M20Avp Shimadzu), equipped with a Phenomenex (Torrance, California, USA) Luna C18 chromatographic column (4.6 mm×250 mm; 5 µm) operating at room temperature (40 °C). The mobile phase used was methanol/phosphoric acid 1% (47:53) (v/v) at a flow rate of 1.2 ml/min (isocratic flow), injection volume of 20 µl, a monitoring wavelength of 370 nm, and analysis time of 30 min. The experiments were conducted in triplicate. Data analyses were conducted in the Class-VP version 6.14 SP1 Shimadzu software.

Samples of 300 mg of dried extracts were dissolved in 5.0 ml of 1:1 (v/v) ethanol: water, and stirred with a magnetic stirrer for 10 min. Then 1 ml of hexane was added to a 1 ml sample of extract and centrifuged for 10 min. The hexane phase was ruled out and 500 µl of the resulting extract was added to 9 ml of dichloromethane and centrifuged for 10 min. Finally, 4 ml of this phase was evaporated and reconstituted in 2 ml of methanol and filtered before injection into the HPLC.

Determination of the drying process yield

Process yield (PY, % w/w), or powder recovery, was calculated immediately after the drying experiments based on the ratio of the powder mass (dry basis) collected in the flask (W) to the portion of the extract feed mass (WE) that was equivalent to the solid content of CSD added by Equation (1).

Statistical analysis

The data were analyzed with the aid of the Statistic 7.0 software program (Statsoft Inc., Tulsa, OK, EUA). The results were expressed as mean±SD and coefficient of variation. The means were compared using ANOVA associated with response surface methodology. Statistical significance was established through a p-value, of which values lower than 0.05 indicate that the factor impact is significant with at least 95% confidence [28].

Accelerated stability study

The stability testing of the dry extract of M. urundeuva obtained in the best drying condition was conducted under a temperature of 40 °C (±2 °C),a relative humidity of 75% (±5%), and controlled by a Tecnal, B. O. D. TE-371 climate chamber (João Pessoa, Brazil) for 6 mo (29). Nine samples with approximately 3g of dried product were placed in hermetic PVC–Aluminum sachets. Quercetin analyses in three samples of the extract were performed at 0, 3 and 6 mo.

Anti-inflammatory activity

The anti-inflammatory activity of the dry extract of M. urundeuva (ES) obtained in the best drying condition was assessed in male Swiss mice (32±5g) using the carrageenan-induced paw edema model [30]. Paw edema was induced by injecting 0.1 ml of 1% (w/v) carrageenan suspended in either saline into sub-plantar tissues of the left hind paw of each mouse. Mice were divided into four groups, each consisting of six animals that received orally the ES dissolved in water by gavage at doses equivalent to 500 mg/kg and 2000 mg/kg of the dried vegetable drugs carefully adjusted to the quantity of dry extract, either saline and diclofenac sodium (10 mg/kg) as standard reference. After one hour, a volume of 0.1 ml of carrageenan (1% w/v) was applied in the subplantar region of the right hind paw of the animals to induce edema. The paw thickness was measured before injecting the carrageenan and after 1, 2, 3, and 4h using vernier caliper. This project was approved by the Ethics Committee on Animal Research of the Federal University of Paraíba (UFPB) (Protocol No. 0207/10) and all the animals used were from the Vivarium of the Center for Biotechnology of the UFPB. The anti-inflammatory activity was calculated as the percentage inhibition of the edema in the animals treated with extract under test in comparison to the carrageenan control group using Equation (2).

Where Tt is the paw thickness of mice given the test extract at a corresponding time and To is the paw thickness of mice of the control group at the same time.

RESULTS

Evaluation of the drying parameters

Table 2 shows the results of the 23+1 factorial experimental design that involved the following variables: the drying air inlet temperature, the flow rate of the drying composition fed to the spray drying, and the proportion of CSD.

Table 2: Evaluation of the drying parameters in dry extracts of M. urundeuva obtained by spray drier

Drying parameters (CSD/inlet temperature/feed rate) Process yield (%)* Quercetin (µg/ml)*
20% 160 °C 8 ml/min 37.9+0.06 20.1+0.4
20% 160 °C 4 ml/min 37.1+0.04 19.8+0.2
20% 180 °C 8 ml/min 41.2+0.06 20.8+0.2
15% 170 °C 6 ml/min 39.5+0.08 21.4+1.1
10% 180 °C 4 ml/min 40.9+0.03 23.3+1.4
20% 180 °C 4 ml/min 40.9+0.04 20.8+1.0
10% 180 °C 8 ml/min 39.1+0.07 23.0+0.7
10% 160 °C 4 ml/min 42.7+0.06 23.2+0.5
10% 160 °C 8 ml/min 44.5+0.06 21.7+0.4

* Values represent the mean±Standard deviation (𝑛 = 3/group). CSD: proportion of colloidal silicon dioxide.

Statistical analyses were performed by ANOVA and multiple linear regression using the response surface methodology to evaluate the effect of the factors on the process yield and concentration of quercetin in dry extracts of M. urundeuva. A significance value of p<0.05 was established and values lower than this were ignored. A summary of the main effects and their significance values are provided in table 3.

Fig. 1 shows the response surface of quercetin concentration in the dried extract of M. urundeuva as a function of the extract feed rate and inlet temperature, which are important factors in the drying process that directly influence product characteristics.

Assessing the degree of influence of these factors can help achieve greater efficiency in the drying process.

Table 3: Summary of significance (ANOVA) of the effect of the independent variables on the responses analysed in factorial design when obtaining dry extracts

Independent variables P-value
Process yield Quercetin content
Inlet Temperature 0.464907 0.000340
Feed rate 0.767776 0.006605
CSD 0.367157 0.207443
Inlet Temperature*Flow rate 0.470684 0.000285
Inlet Temperature*CSD 0.685150 0.000035
Feed rate*CSD 0.301538 0.263401
Inlet Temperature*Feed rate*CSD 0.797260 0.010428

CSD: proportion of colloidal silicon dioxide.


Fig. 1: Response surface of quercetin concentration in M. urundeuva dried extract as a function of the extract feed rate and inlet temperature


Fig. 2: Concentration of quercetin in spray dried extract stored during the stability test (𝑛 = 3/group)

Accelerated stability study

Fig. 2 shows the concentrations of quercetin in extract samples stored at 40 °C (±2 °C) and 75% (±5%) during the stability testing period of 6 mo.

Anti-inflammatory activity

Table 4 shows the results of the anti-inflammatory effect of the dry extract of M. urundeuva (DEMU) administered by oral route in mice evaluated by the method of paw edema induced by carrageenan.

Table 4: Effect of dry extracts of M. urundeuva in the paw edema induced by carrageenan in mice

Time (h) Difference between the right and left paws (mm) Inhibition (%)
CG 1% DICLO 10 mg/kg ES 500 mg/kg ES 2000 mg/kg DICLO 10 mg/kg DEMU
500 mg/kg		 DEMU
2000 mg/kg
0 0.1+0.2 0.0+0.1 0.0+0.1 0.0+0.1 - - -
1 1.4+0.2 0.8+0.4*** 0.8+0.2*** 0.4+0.4*** 46.4 49.0 69.0
2 1.6+0.3 0.7+0.2*** 0.7+0.3** 1.2+0.5*** 59.8 60.2 26.8
3 1.2+0.3 0.6+0.2** 0.6+0.3*** 1.0+0.3*** 53.4 37.8 20.5
4 1.4+0.3 0.6+0.2** 0.6+0.3*** 1.1+0.3*** 59.3 43.9 16.0

Values represent the mean of difference of paw measure±Standard deviation (n = 6/group). Statistically different from the control group, ** p<0.01, ***P<0.001 (ANOVA followed by Student Newman-Keuls test). DEMU: Dry extract of M. urundeuva, DICLO: Diclofenac sodium, CG: carrageenan.

DISCUSSION

Evaluation of the drying parameters

According to table 2, the results of the 23+1 factorial experimental design involving the variables drying air inlet temperature, flow rate of the drying composition fed to the spray drying, and the proportion of CSD showed that variations in these drying parameters did not result in major changes in process yield or the quercetin levels in dry extracts, but evaluating the effect and significance of these factors on the process yield and concentration of quercetin, statistical analyses were performed by ANOVA and multiple linear regression using the response surface methodology.

As shown in table 3, the independent variables (drying temperature, feed rate and proportion of CSD) did not significantly affect the process yield (p>0.05). However, the drying temperature and feed rate significantly influenced the concentration of quercetin (p≤0.05). The analysis of the response surface of the quercetin concentration data in dry extracts showed that as the temperature was increased in association with an increase in the feed rate of input material, the concentration of quercetin also increased (fig. 1).

This indicated that at a temperature of 180 °C and a feed rate of 8 ml/min resulted in an increase in drying efficiency. During the process of drying plant extracts, the increase in temperature generally reduces the surface tension and viscosity of the input material, facilitating the formation of droplets and resulting in higher quality products [31, 32]. Proper adjustment of the feed speed enables the droplets to evaporate before they come into contact with the walls of the drying chamber, preventing the accumulation of material on the chamber walls [33, 34]. Secondary interactions were also observed between the inlet temperature and the CSD (p≤0.05), which may have occurred because the temperature variable displayed high significance and the proportion of CSD reacted, making this interaction significant. This was also found upon evaluating the tertiary interaction of the three factors that were significant (p≤0.05) due to the significant variables drying temperature and feed rate [35].

The increase of temperature and feed rate favored the concentration of quercetin in dry extracts, while the proportion of CSD had no significant influence, so the extract obtained with a 10% proportion of CSD, 180 °C inlet temperature and 8 ml/min feed rate was chosen to perform the accelerated stability study and evaluation of anti-inflammatory activity.

Accelerated stability study

An accelerated stability study was performed to better characterise the dry extract of M. urundeuva and monitor quercetin markers for a longer period of time. The stability of pharmaceutical products is essential for assessing the maintenance of quality and efficiency of products during the period and conditions storage, especially of plant products that are more susceptible to physical, chemical and microbiological changes.

Fig. 2 showed the concentrations of quercetin in extract samples stored at 40 °C (±2 °C) and 75% (±5%) during the stability testing period of 6 mo. There was an increase in the value of the concentration of quercetin after 3 mo (69.2 µg/ml) compared to the initial concentration (51.5 µg/ml), though this remained stable (67.4 µg/ml) after 6 mo. This may have occurred due to the evaporation of volatile components present in the extract and moisture loss resulting in increased concentration of quercetin [36].

Thus this study indicated that the drying process by spray dryer resulted in stable extracts dried relative to the preservation of their chemical constituents and the quercetin showed stable physical and chemical characteristics, making it a suitable biomarker for monitoring the studied processes.

Anti-inflammatory activity

Table 4 showed the results of the anti-inflammatory effect of the dry extract of M. urundeuva (ES) administered by oral route in mice evaluated by the method of paw edema induced by carrageenan. The inhibitions of the paw edemas were significantly different between the groups of diclofenac sodium and the groups that were administered two dosages of the extracts (p<0.05). At a dose of 500 mg/kg, the highest percentage of inhibition of edema was observed at 2 h, while the highest percentage of inhibition of edema was observed at one hour for a dose of 2000 mg/kg. Carrageenan is an inflammatory agent that elicits the inflammatory process and hence the formation of edema through the release of histamine, serotonin, bradykinin, and prostaglandins [3, 37-39]. Thus it is possible that compounds present in the M. urundeuva extract interfere with the inflammatory process mediated by these substances. Several studies have demonstrated the anti-inflammatory activity of extracts of M. urundeuva [3, 40-42]. This study showed the drying process by spray drier maintained chemical constituents of the extract responsible for anti-inflammatory activities of the plant.

CONCLUSION

The spray dryer technique proved to be adequate in obtaining dry extracts of M. urundeuva and variations in the proportion of CSD, inlet temperature, and the feed rate showed no significant variations in the drying process yield. Statistically, the study found positive a contribution to the inlet temperature and the feed rate over the concentration of quercetin on the responses analyzed, so that a 10% proportion of CSD, a 180 °C inlet temperature and an 8 ml/min feed rate was considered the most suitable condition for obtaining the dry extracts of M. urundeuva.

The dried extracts showed anti-inflammatory activity and the stability study indicated that the drying process by spray drying resulted in dry extracts with stable chemical constituents. In addition, the biomarker quercetin was stable during the drying process and satisfactory for monitoring and providing quality control of M. urundeuva extracts in the development of herbal products with this plant.

ACKNOWLEDGEMENT

The authors acknowledge the fellowships received from Conselho Nacional de Pesquisa (CNPq).

CONFLICT OF INTERESTS

Declared none

REFERENCES

  1. Santin DA, Leitão Filho HF. Restabelecimento e revisão taxonômica do gênero Myracrodruon Freire Allemão (Anacardiaceae). Revista Brasileira de Botânica 1991; 14:133-45.
  2. Rao VS, Viana GS, Menezes AMS, Gadelha MG. Studies on the antiulcerogenic activity of Astronium urundeuva Engl. II. aqueos extract. Braz J Med Biol Res 1987;20:803-5.
  3. Souza SMC, Aquino LCM, Jr ACM, Bandeira MAM, Nobre MEP, Viana GSB. Antiinflammatory and antiulcer properties of tannins from Myracrodruon urundeuva Allemão (Anacardiaceae) in rodents. Phytother Res 2007;21:220–5.
  4. Carlini EA, Duarte-Ameida JM, Rodrigues E, Tabach R. Antiulcer effect of the pepper trees Schinus terebinthifolius Raddi (aroeira-da-praia) and Myracrodruon urundeuva allemão, anacardiaceae (aroeira-do-sertão). Rev Bras Farmacogn 2010;20:140-6.
  5. Viana GSB, Bandeira MAM, Moura LC, Souza Filho MVP, Matos FJA, Ribeiro RA. Analgesic and antiinflammatory effects of the tannin fraction from Myracrodruon urundeuva Fr. All Phitoter Res 1997;11:118-22.
  6. Sá RA, Argolo ACC, Napoleão TH, Gomes FS, Santos NDL, Melo CML, et al. Antioxidant, fusarium growth inhibition and nasutitermes corniger repellent activities of secondary metabolites from Myracrodruon urundeuva heartwood. Int Dech Monog 2009;63:470-7.
  7. Nobre-Júnior HV, Oliveira RA, Maia FD, Nogueira MAS, Moraes MO, Bandeira MAM, et al. Neuroprotective effects of chalcones from Myracrodruon urundeuva on 6-Hydroxydopamine-induced cytotoxicity in rat mesencephalic cells. Neurochem Res 2009;34:1066-75.
  8. Mahmoud TS, Marques MR, Pessoa CÓ, Lotufo LVC, Magalhães HIF, Moraes MO, et al. In vitro cytotoxic activity of Brazilian Middle West plant extracts. Rev Bras Farmacogn 2011;21:456-64.
  9. Souza SMC. Padronização de extratos vegetais: Astronium urundeuva (Anacardiaceae). Dissertação de mestrado, Universidade Estadual Paulista, Araraquara; 2012.
  10. Monteiro JM, Lins Neto EMF, Amorim ELC, Strattmann RR, Araújo EL, Albuquerque UP. Teor de taninos em três espécies medicinais arbóreas simpátricas da caatinga. Rev Arvore 2005;29:999-1005.
  11. Silva MD. Estudo farmacobotânico de três espécies medicinais da caatinga em pernambuco. Dissertação de Mestrado. Universidade Federal Rural de Pernambuco, Recife; 2008.
  12. Muthukala B, Sivakumari K, Ashok K. Antioxidant and anti-inflammatory potential of qucertin. Int J Curr Pharm Res 2015;7:758-79.
  13. Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY, et al. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 2011;218:44–52.
  14. Anitha T. Medicinal plants used in skin protection. Asian J Pharm Clin Res 2012;5:35-8.
  15. Rattanachaikunsopon P, Phumkhachorn P. Contents and antibacterial activity of flavonoids extracted from leaves of Psidium guajava. J Med Plants Res 2010;4:393–6.
  16. Jandú JJB, Silva LCN, Pereira APC, Souza RM, Silva Júnior CA, Figueiredo RCBQ, et al. Myracrodruon urundeuva bark: an antimicrobial, antioxidant and non-cytotoxic agent. J Med Plants Res 2013;7:413-8.
  17. Simões VN, Favarin LRV, Cabeza NA, Oliveira TD, Fiorucci AR, Stropa JM, et al. Síntese, caracterização e estudo das propriedades de um novo complexo mononuclear contendo quercetina e íon Ga(III). Quim Nova 2013;36:495-501.
  18. Aguado MI, Núñez MB, Dudik HN, Bela A, Raisman JS, Sansberro P. Diseño de coprimidos de extrato de Aloysia polystachya por compressión directa. Latt Am J Pharm 2006;25:225-30.
  19. Carvalho ACB, Balbino EE, Maciel A, Perfeito JPS. Situação do registro de medicamentos fitoterápicos no Brasil. Rev Bras Farmacogn 2008;18:314-9.
  20. Oliveira OW, Petrovick PR. Secagem por aspersão (spray drying) de extratos vegetais: bases e aplicações. Rev Bras Farmacogn 2010;20:641-50.
  21. Broadhead J, Rouan SKE, Rhodes CT. The spray drying of pharmaceuticals. Drug Dev Ind Pharm 1992;18:1169-206.
  22. Teixeira HF. Avaliação da influência de adjuvantes farmacêuticos sobre as características físicas, químicas, tecnológicas e farmacológicas de extratos secos nebulizados de Achyrocline satureioides (Lam.) DC. Compositae–Marcela. Caderno de Farmacia 1997;13:151-2.
  23. Cunha AM, Menon S, Menon R, Couto AG, Bürger C, Biavatti MW. Hypoglycemic activity of dried extracts of Bauhinia forficata Link. Phytomedicine 2010;17:37-41.
  24. Gallo L, Llabot JM, Allemandi D, Bucalá V, Piña J. Influence of spray-drying operating conditions on Rhamnus purshiana (Cáscara sagrada) extract powder physical properties. Powder Technol 2011;208:205-14.
  25. Rowe RC, Sheskey PJ, Owen SC. Handbook of pharmaceutical excipientes. Londom/Chicago: Pharmaceutical Press; 2006.
  26. American Chemical Society (ACS). Subcommittee on Environmental Analytical Chemistry. Guidelines for data acquisition and data quality evaluation in environmental chemistry. Anal Chem 1980;52:2242-9.
  27. ICH Q2B. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation Research. Guidance for industry: ICH Q2B Validation of analytical procedures: methodology. Rockville; 1995.
  28. Anderson MJ, Whitcomb PJ. DOE Simplified. Practical Tools for Effective Experimentation. Seconded. Productivity Press: New York; 2007.
  29. ICH Q1A R2. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation Research. Guidance for industry: Q1A (R2) Stability Testing of New Drug Substances and Products. Rockville; 2003.
  30. Winter CA, Risley EA, Nuss GW. Carrageenin-induced edemas in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 1962;111:544-7.
  31. Cortés-Rojas DF, Souza CRF, Oliveira WP. Optimisation of spray drying conditions for production of Bidens pilosa L. dried extract. Chem Eng Res Des 2015;93:366-76.
  32. Soares LAL. Obtenção de comprimidos contendo alto teor de produto seco por aspersão de Maytenus ilicifolia Mart. ex Reissek-Celastraceae. Desenvolvimento tecnológico de produtos intermediários e final. Tese de doutorado, Programa de Pós-graduação em Ciências Farmacêuticas, UFRGS, Porto Alegre; 2002.
  33. Masters K. Spray Drying Handbook. Londres: George Godwin; 1985.
  34. Rankell AS, Lieberman HÁ, Schiffman RF. Secagem. In: Lachman L, Lieberman HA, Kanig JL. Teoria e prática na indústria farmacêutica. Lisboa: Calouste Gulbenkian; 2001. p. 83-112.
  35. Cardoso NQ. Desenvolvimento tecnológico de extratos vegetais padronizados a partir da Lafoensia pacari A. St.-Hill (Lythraceae). Dissertação de Mestrado, Programa de Pós-graduação em Ciências Farmacêuticas, UFG, Goiânia; 2013.
  36. Florence AT, Attwood D. Physicochemical Principles of Pharmacy. London: Pharmaceutical Press (Php); 2006.
  37. Di Rosa M, Giroud JP, Willoughby DA. Studies on the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol 1971;104:15-28.
  38. Niazi J, Gupta V, Chakarborty P, Kumar P. Antiinflammatory and antipyretic activity of Aleuritis moluccana leaves. Asian J Pharm Clin Res 2010;3:35-7.
  39. Babu AS, Karki SS. Anti-inflammatory activity of various extracts of roots of Calotropis procera against different inflammation models. Int J Pharm Pharm Sci 2011;3:191-4.
  40. Bandeira MAM, Matos FJA, Braz-Filho R. New chalconoid dimers from Myracrodruon urundeuva. Nat Prod Lett 1994;4:113-20.
  41. Viana GSB, Bandeira MAM, Matos FJA. Analgesic and antiinflammatory effects of chalcones isolated from Myracrodruon urundeuva Allemão. Phytomedicine 2003;10:189-95.
  42. Viana GSB, Bandeira MAM, Moura LC, Souza Filho MVP, Matos FJA, Ribeiro RA. Analgesic and antiinflammatory effects of the tannin fraction from Myracrodruon urundeuva Fr. All Phitoter Res 1997;11:118-22.

How to cite this article