Formulation of Capsule Dosage Form Containing Ethanolic Fruit Extract of Terminalia chebula Retz. (Hpan-ga) Having Potent Antioxidant Activity
Wai Wai Lwin, Cho Yi Myint, Maung Maung & Khin Tar Yar Myint
Myanmar Health Sciences Research Journal, Vol. 32, No. 1, 2020Abstract
Recently, the usefulness of medicinal plants in health care delivery has been emphasized and WHO recognizes and endorses the use of those which have been scientifically proven to be efficacious, safe for use and of good quality. Thus, it is necessary to formulate these valuable herbal medicinal plants into dosage form. This study is aimed to formulate the capsule dosage form containing 75% ethanolic fruit extract of Terminalia chebula Retz. (Hpan-ga) having antioxidant activity. Prior to formulation into capsule dosage form, physicochemical and phytochemical characterization were investigated and all were complied with the specified limits prescribed in the Pharmacopoeias. In addition, according to the Folin-Ciocalteu colorimetric method, the total polyphenol content of 75% ethanolic extract was 270.664 mg GAE/g and IC50 value obtained from DPPH radical scavenging test was 0.238 mg/mL. Thus, ethanolic extract having antioxidant activity was formulated into capsule dosage form using four different formulations containing adsorbent-loaded dried extract. The pharmaceutical evaluation studies revealed that among different formulations, microcrystalline cellulose (MCC)-loaded dried extract capsule containing 3% talc showed short disintegration time (p<0.05), good uniformity of weight and dissolution. Thus, according to the study, capsule containing MCC-loaded dried extract granules with considerable amount of total polyphenol content showed reproducible capsule dosage form having antioxidant activity.Go to : Goto
In recent years, plant-derived products are increasingly used as medicinal products, nutraceuticals and cosmetics. Less toxicity, better therapeutic effect, good patient compliance and cost effectiveness are the reasons for choosing drug from natural origin. Among the herbal medicinal products, the global interest is the usefulness of antioxidant activity in herbal medicine. Inhibition of free radical-induced oxidative damage by supplementation of antioxidants has become an attractive therapeutic strategy for reducing the risk of diseases. Among natural antioxidant, phenols and polyphenols are promising phytochemical as important class of natural products having multiple polar functionality and a variety of effects towards antioxidant behavior. In Myanmar, there are many indigenous medicinal plants which claimed traditionally for health benefits. Among these, Terminalia chebula Retz. (Combretaceae) is well-known plant in Myanmar and is called Hpan-ga. Because of several medicinal properties attributed to Terminalia chebula Retz., it is used extensively in the preparation of many Ayurvedic formulations. The antioxidant activity is promising in the fruit of Terminalia chebula Retz. because of the major constituent of tannin (32%) especially hydrolysable tannin such as gallic acid, ellagic acid and corilagin which are natural polyphenols possessing strong antioxidant, anticancer, antimicrobial, and anti-inflammatory vactivities.1 However, according to Fang & Bhandari (2010), these valuable natural compound’s uses are substantially limited because of their instability during food processing, distri- bution or storage.2 Other problems in relation with uses of polyphenol in human health are unpleasant taste which must be masked before their incorporation in foodstuffs or oral medicines. Therefore, the administration of phenolic compounds requires the formulation of a finished protecting product able to maintain the structural integrity of the polyphenol until the consumption or the administration, mask its taste, increases its water solubility and bioavailability.
For efficacy of
the medicinal plant, not only the effectiveness of the plant or extract on the
treatment but also the presentation of the dosage form are needed to be
considered. Although the most common dosage forms
of herbal preparations are liquids derived from macerations, infusions and decoctions,3 this type of dosage forms have some associated problems of large dose volumes, impractical packaging and poor stability.4 Solid preparations on the other hand often have higher stability and are easier to standardize which adds to an increase in
their therapeutic acceptance, efficacy and product value.5
Among oral solid dosage form, capsule dosage form is preferred. This may be due to the fact that capsule dosage form needs not much formulation steps and it may give protection of ingredients from environmental condition. Moreover, these dosage form can mask the bitter taste and unpleasant smell of herbal extract.
The identification of the active compounds in the herbal medicine is important to know how much the active components intake by patient for single doses. Therefore, the standardization of the total polyphenols content in dosage form is important factor.
MATERIALS AND METHODS
MATERIALS AND METHODS
Investigation of phytochemical and physi- cochemical study
The present study was laboratory-based analytical study. The fresh mature fruits of Terminalia chebula Retz. were collected from Magway Division in May and the authenticity was confirmed by competent botanist. The preliminary phytochemical screenings were qualitatively determined according to Harbone (1984) 6 and the physi- cochemical properties of T. chebula Retz. were assessed according to the quality control methods for medicinal plant materials.7, 8 The analysis was conducted at University of Traditional Medicine, Mandalay.
Extraction of fruits of Terminalia chebula Retz.
to the previous study, the 75% ethanol was found to be the suitable solvent for
extraction of T. chebula fruit to
obtain high amount of total polyphenol.9 Dried powder was extracted
with 75% ethanol by cold maceration process for 7 days. Then, 75% ethanolic
extract was filtered and con- centrated at 40ºC under reduced pressure
by rotary evaporator. The obtained liquid extract was then dried on water bath at 50°C for 48 hours until the concentrated viscous extract was obtained.
Acute oral toxicity test
The ethanolic extract of T. chebula Retz. was tested for acute toxicity according to Organization of Economic Cooperation and Development guideline 42510 which was performed at Pharmacology Research Division, Department of Medical Research, Yangon. According to the literature, the ethanolic extract of Terminalia chebula Retz. is likely to be non-toxic.11 Therefore, limit test at 5000 mg/kg was performed.
Determination of total phenol contents in the ethanolic fruit extract of T. chebula Retz
The major constituent that gives antioxidant activity of Terminalia chebula fruit is total polyphenol. This experiment was carried out according to Celep, Aydin & Yesilada (2017) with some modification.12 Determination of total phenolic compounds was done by Folin Ciocalteu colorimetric method and the absorbance was measured at 765 nm with UV-Vis spectrophotometer. Then, the results were expressed as gallic acid equivalent (GAE) (n=3).
Determination of in vitro antioxidant activity of ethanolic extract by DPPH radical scavenging assay
Antioxidant activitiy of ethanolic extract was determined by in vitro DPPH method according to Vieira et al. (2013) with some modification.13 The ascorbic acid was used as standard. The sample solutions were prepared by dissolving the extract in 75% ethanol to obtain the concentrations of 10, 40, 80, 120, 160, 200 µg/mL, respectively. To 2.9 mL of DPPH (60µM) solution, 0.1 mL of extracts with different concent- rations were added and mixed vigorously by a vortex mixer. All solutions were allowed to stand at room temperature for 30 minutes in the dark and measurement of absorbance was done at 517 nm using a UV-Vis spectro- photometer. The percent inhibition was calculated by using the following formula.
Go to : Goto
We would like to express our thanks to Rector (University of Pharmacy) who give permission to conduct this research, Dr. Khin Phyu Phyu (Department of Medical Research), Daw Mu Mu Sein Myint, (Department of Medical Research), Dr. Kyi Kyi Oo, University of Traditional Medicine and staff from Pharmaceutical Chemistry Laboratory (Department of Food and Drug Administration). We are also grateful to all who helped and gave suggestions to complete this research.Go to : Goto
CONFLICT OF INTEREST
CONFLICT OF INTEREST
The authors declare that they have no competing interests.Go to : Goto
1. Itsarasook K, Ingkaninan K, Chulasiri M & Viyoch J. Antioxidant activity and cytotoxic- city to human skin fibroblasts of Terminalia chebula fruit extract. International Conference on Biological and Life Sciences 2012; 40: 43-46.
2. Fang Z & Bhandari B. Encapsulation of polyphenols - A review. Trends Food Science Technology 2010; 21(10): 510-523.
H, Yogesh HS, Goplakrishna B, Chandrashekhar VM, Sathish kumar BP
& Vadlapudi K. An overview of herbal medicine. International Journal of Pharma- ceutical Sciences 2009; 1(1): 1-20.
4. Okunlola A, Babatunde AA & Oluwatoyin AO. Evaluation of pharmaceutical and microbial qualitities of some herbal medicinal products in South Western Nigeria. Tropical Journal of Pharmaceutical Research 2007; 6(1): 661-670.
Runha FP, Cordeiro DS, Pereira
CAM, Vilegas J & Oliveira WP. Production of dry extracts of medicinal brazilian
plants by spouted bed process: Development of
the process and evaluation of thermal degradation during the drying operation. Food Bioproduct and Process 2001; 79(3): 160-168.
6. Harbone JB. Phytochemical Method. 2nd ed, Chapman and Hall: New York. 1984.
7. World Health Organization. Quality Control Methods for Medicinal Plant Materials. WHO Geneva, 2011.
8. UNANI Physicochemical Standards of UNANI Medicines Formulations. New Delhi, Central council for research in UNANI Medicine, Ministry of Health and Family Welfare, 1987; 274-292.
9. Wai Wai Lwin, Maung Maung, Cho Yi Myint, & Khin Tar Yar Myint. Influence of drying method and solvent concentration on the content of total polyphenol in Terminalia chebula Retz. fruit extract. Second Con- ference on Pharmacy Research 2018 May, Yangon, Myanmar.
10. OECD Test No. 425. Acute Oral Toxicity- Up-and-Down-Procedure. OECD guideline for testing of chemicals Section 4. OECD Publishing, Paris, 2008. [Internet] Avialable from [https://doi.org/10.1787/97892640710
11. Amutha M, Geetha A & Amutha M. A pilot study on the determination of antioxidant potential and lethal dosage of hydro alcoholic fruit extract of Terminalia chebula. Inter- national Journal of Pharmacy and Pharma- ceutical Sciences 2014; 6(6): 346-351.
Aydin A & Yesilada E. A com- parative study on the in vitro antioxidant
potentials of three edible fruits: Cornelian cherry, Japanese persimmon and
cherry laurel. Food and Chemical
2017; 50: 3329-3335.
GS, Cavalcanti RN, Meireles MAA & Hubinger MD. Chemical and economic evaluation of natural antioxidant
extracts obtained by ultrasound-assisted and
agitated bed extraction from jussara pulp (Euterpe edulis). Journal of Food Engineering 2013; 19(2): 196-204.
P, Suttajit M. & Pongsawat- manit R. Assessment of phenolic content and free
radical scavenging capacity of some
Thai indigenous plants. Food Chemistry 2007; 100(4): 1409-1418.
15. Lee HS, Woon NH, Kim KH, Lee H, Jun W & Lee KW. Antioxidant effects of aqueous extract of Terminalia chebula in vivo and in vitro. Biological and Pharmaceutical Bulletin 2005; 28(9): 1639-1644.
16. Kumadoh D, Adotey J, Ofori-Kwakye K, Kipo SL, Prah T & Patterson S. Formulation of oral capsules from Asena herbal decoction used traditionally in Ghana for the treatment of arthritis. World Journal of Pharmacy and Pharmaceutical Sciences 2014; 3(7): 1824-33.
Uwaezuoke OJ, Bamiro OA, Ngwuluka NC, Ajalla OT
& Okinbaloye AO. Comparative evaluation of the disintegrant properties
of rice husk cellulose, corn starch and Avicel in Metronidazole tablet formulation. Journal of Applied Pharmaceutical Science 2014; 4(12): 112-117.
18. Peck GE, Baley GJ, McCurdy VE & Banker GS. Tablet formulation and design. In: Pharmaceutical Dosage Forms: Tablets. Lieberma HA, Lachman L, Schwatz JB (Eds), 2nd ed. New York: Marcel Dekker, Inc; 1989; 75-130.19. British Pharmacopoeia. The General Medical Council, vol. 4, .The Pharmaceutical Press, London, 2016.