IDENTITAS JURNAL
1 Nama Jurnal Indonesian Journal of Pharmacy
2 Website Jurnal http://indonesianjpharm.farmasi.ugm.ac.id/index.php/3 3 Status Makalah Submitted
4 Jenis Jurnal Jurnal Nasional Terakreditasi 4 Tanggal Submit 13 Desember 2018
5 Bukti Screenshot Submit
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DAFTAR PUSTAKA
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Lampiran 1. Artikel yang disubmit ke Jurnal Nasional Terakreditasi
COMPARISON USE OF EUGENOL AND OLEIC ACID AS PLASTICIZER ON CHARACTERISTICS OF HYDROBROMIDE
DEXTROMETORPHAN EDIBLE FILM
Nining1*, Rahmah Elfiyani1, Elvira Wulandari
1. Faculty of pharmacy and science, Universitas Muhammadiyah Prof. DR.
Hamka, Jl. Delima II/IV, Jakarta Timur, 13460 Submitted:
Revised:
Accepted:
*Corresponding author Author Correspondent Email: nining@uhamka.ac.id Email Correspondent
ABSTRACT
Dextrometorphan hydrobromide is a cough suppressing drug as strong as codein but last longer. Formulation of edible film added oleic acid and eugenol as plasticizer to improve tensile strength and elongation. This study aims to compare the influence of plasticizer usage against characteristic of dextromethorphan hydrobromide edible film. The study began with produce dextromethorphan hydrobromide edible film using the comparative use of oleic acid and eugenol on the concentration 2%, 4% and 6%. Each formula evaluated organoleptically, uniformity of weight, thickness, tensile strength and elongation, pH, disintegration time, determination of drug, and uniformity of content. The results showed that edible film with eugenol has higher tensile strength and elongation than with oleic acid. From the results, it can be concluded that eugenol as plasticizer produce better characteristic than oleic acid at a concentration of 2%, 4% and 6% against dextromethorphan hydrobromide edible film.
Key words: Dextrometorphan HBr, Edible film, Eugenol, Oleic acid, Plasticizer
INTRODUCTION
Coughing is a reflex physiology protection to press and clean the respiratory tract of phlegm, dust and other foreign particles (Tan and Raharja 2013). One of the active substances that are used to treat cough circulating in the market is dextrometorphan hidrobromide. Dextrometorphan hidrobromide be formulated into dosage forms of an alternative that is unique and practical, namely edible film, where edible film can be quickly dissolved in the mucosa of the mouth making it easier to consume.
Edible film is a thin sheet made from edible materials among other carbohydrates (starch, pectin, carrageenan, alginat, and gum), protein and fat, or a combination of both. This shaped thin sheet material consumed was placed above the tongue then left active substances dissolves so regardless in the oral cavity (Krochta 1994). Pectin of pomelo skin as film is able to form good gel, elastic, edible, and can be renewed. Even so, pectin of pomelo skin film has disadvantage, that film is not too strong compared to other films of the
polysaccharide. While chitosan produces film that is strong, elastic, flexible and tough torn down. Edible film composed of pomelo skin pectin can produce film but the film was not strong enough and are easy fragile, so that needs to be added to strengthen chitosan so that the resulting film is strong and not easily fragile but are rigid. So as to increase the elasticity of the film needs to be added plasticizer (Suprioto F 2010). One of the plasticizer that could be used i.e. vegetable oils.
Vegetable oils are selected in this study i.e., eugenol and oleic acid. Wahyuningtyas (2015) has been conducting research on the addition of plasticizer oleic acid on starch cassava/chitosan can affect physical properties of films, particularly increasing tensile strength and elongation percent. From results of the study, oleic acid with concentration of 1% can improve characteristics of edible films. Other research mentions, eugenol usage as plasticizer can increase tensile strength and elongation percent, extending water vapor permeability (Verona S 2014). From results of such research, eugenol 5% is able to improve the
44 characteristics of edible films. Then on this research, the use of eugenol and oleic acid at the same concentration (2%, 4% and 6%) as the plasticizer can increase the tensile strength and elongation percent preparations edible films.
MATERIAL AND METHODS
Tools used in this research include analytical balance (OHAUS), glass mold edible film, magnetic stirrer (MS-H-PRO), tensile testing machine (Strograph RJ,Toiseki), micrometer, oven (Memmert), pH meter (LaMotte), desiccator, furnace (Barnstead Thermolyne), ultrasonic (Ney ultrasonik), spectrophotometer UV-Vis (Shimadzu UV- 1601), and sieve no. 80.
The materials used in this research is dextrometorphan hidrobromide (Divislab), pomelo skin pectin, chitosan (Monodon group), acetic acid (PT. Putra Primajaya), oleat acid (Sigma-Aldrich), eugenol (Sigma-Aldrich), sucrose (Cap-Bintang Indonesia), menthol (PT.
Samiraschem), nipagin (Ueno-Japan), nipasol (Ueno-Japan), ethanol (PT. Molindo Raya Industrial), dan aquadest (Harum Kimia).
Manufacture and Evaluation Pectin from Skin of Pomelo
In preparing pectin, 25 grams powder pomelo skin weighed. 250 ml water and 10 ml HCl 1 N were added to reflux flask and heated at 80°C for 120 minutes. Extract solution filtrated by drab fabric into beaker glass. Filtrate was cooled and precipitated 1:1 with alcohol 96% for 24 hours. The precipitant was separated from the aqueous solution by filtration using a filter paper and washed with alcohol 96% to remove residual acid. Pectin gel was dried in oven at 45°C for 8 hrs and weighed.
Organoleptic test
Organoleptic test was observed of microscopic and senses include shape, smell, and color.
Identification test of pectin
1) 1 grams pectin was added 9 ml water, then heated above steam until the formed solution, then replace the lost evaporation water until a stiff gel formed.
2) 0.5 grams pectin was added 50 ml water and stir until dissolved. Solution added ethanol P in the same volume until clear precipitate formed, such as gelatin.
3) 5 ml solution (0.5 in 50) was added 1 ml NaOH 2N and kept at room temperature for 15 minutes until gel or semi gel formed.
4) Gel from previous test was acidified with hydrochloric acid 3N. Solution was shake and precipitant formed such as gelatin, colorless and spread, which become white and agglomerate when heated.
Content of ash test
Porcelain vials was heated on bunsen for 1 hour, burned in furnace at 5500°C for 1 hours and weighed. Sample was weighed in 3 grams, heated, and burned same as empty porcelain vials. Ash was cooled in desiccator for 30 minutes and weighed. The process was repeated until the difference last and previous weigh maximum of 1 mg (Depkes RI 1997).
Lost on drying
Sample was weighed 1-2 grams in bottles weigh that have previously heated at 105°C for 30 minutes and has been calibrated. Flatten the sample in the bottles weigh until the layers 5 to 10 mm, dried in oven (the lid was opened) at 105°C until fixed weight (Depkes RI 1997).
Equivalent weight/ EW (Ranganna 1997) Equivalent weights specified with 0.5 grams of pectin was added 5 ml ethanol 96%
and 1 grams NaCl into erlenmeyer flask. 100 ml distilled water free of CO2 and 6 drops indicator pp was added. The mixture was titrated with NaOH 0.1 N until turns into pale pink (pH 7.5) and persisted at least 30 seconds.
Neutral solution was used for the determination of methoxyl levels.
Content of methoxyl
Neutral solution of determination EW was added 25 ml NaOH 0.25 N. Solution beaten and kept for 30 minutes in a closed flask. Then, solution was added again 25 ml HCl 0.25 N and titrated with NaOH 0.1 N until the indicator turns into pale pink.
45
Manufacture and Evaluation of Edible Film from Pectin
Table 1. Formula of Edible film
No Materials Function Formula
F1 F2 F3 F4 F5 F6
1 DMP HBr Drug 300 mg 300 mg 300 mg 300 mg 300 mg 300 mg
2 Pectin Film forming 5% 5% 5% 5% 5% 5%
3 Chitosan Film forming 5% 5% 5% 5% 5% 5%
4 Oleic acid Plasticizer 2% 4% 6% - - -
5 Eugenol Plasticizer - - - 2% 4% 6%
6 Acetic acid Solvent 10 ml 10 ml 10 ml 10 ml 10 ml 10 ml
7 Sucrose Sweeter 8% 8% 8% 8% 8% 8%
8 Menthol Flavors 0,5% 0,5% 0,5% 0,5% 0,5% 0,5%
9 Nipagin Preservative 0,18% 0,18% 0,18% 0,18% 0,18% 0,18%
10 Nipasol Preservative 0,02% 0,02% 0,02% 0,02% 0,02% 0,02%
11 Aquadest ad Solvent 100 ml 100 ml 100 ml 100 ml 100 ml 100 ml Pectin was dissolved with hot distilled
water, then stir until clear gel was formed. The mixture was added chitosan and acetic acid 1%
while stirring using magnetic stirrer at 40°C for 45 minutes. The mixture was mixed with oleic acid until homogeneous (M1). DMP was dissolved with cold water as solvent (M2).
Sucrose, nipagin and nipasol was dissolved with hot water (M3). M1, M2 and M3 were mixed until homogeneous. Menthol with 2-3 drops of ethanol was added to mixture and distilled water. The mixture of all was poured and molded on the glass mold 12×20 cm. Drying was done in oven at 30-40°C for 24 hours, then removed from the mold and cut into pieces the size of 2×2 cm. The step was repeated for the produce edible film with eugenol as plasticizer.
Organoleptic test
Organoleptic test was observed of senses include shape, smell, taste and color.
Uniformity of weights
20 edible film was weighted one by one and calculated the average. Edible film weight should not be more than 2 edibles who does it weigh deviate from its average weights of the value in column A and none does it weigh one edible deviate from the average weights more than the value in column B.
Determination of film thickness
The thickness was measured using a micrometer screw with accuracy 0.01 mm on 5 different points (Lachman et al. 1994).
Tensile strength and elongation
Tensile strength and elongation was measured using tensile tester strograph-R1 style with 100 kg. The film was cut with a Dumbbell Astm-D-1822-L Crosshead (speed of 25 mm/min). Elongation was measured until film break. The resulting data was analyzed statistically.
Disintegrating time
Petri dish (d 10 cm) was filled with 10 ml distilled water. Edible film was placed in the midst of petri dish. Time was calculated that edible film destroyed entirely become soft (resolved) (Bhowmik et al. 2009).
Determination of pH
pH was measured using pH meter that is calibrated in advance using pH buffer 4 and 7.
The electrode was rinsed with distilled water and dried. pH measurements have been performed on the solution of edible to be molded (Suprioto 2010).
Determination and uniformity of content 1) Solution standard and determination of
46 maximum wavelength
50 mg DMP was weighted and dissolved in 500 ml measuring flask (100 µg/ml) with phosphate pH 6.8. Maximum wavelength was measured using UV-Vis spectrophotometer.
2) Calibration curve of DMP
Standard solution was made in variance concentration. Absorption was measured using UV-Vis spectrophotometer.
3) Determination of content
20 sheets of edible film dissolved with buffer phosphate pH 6.8 in 100 ml measuring flask. Solution was sonicated for 30 minutes and filtered. 1 ml filtrate was diluted in 10 ml measuring flask.
Absorption was measured using UV-Vis spectrophotometer.
4) Uniformity of content
10 sheets of edible film dissolved one by one with buffer phosphate pH 6.8 in 100 ml measuring flask. Solution was sonicated for 15 minutes and filtered.
Absorption was measured using UV-Vis spectrophotometer.
Statistically analysis
Data result of tensile strength and elongation edible film from each formula was analyzed using two-way ANOVA by comparing each formula to notice any difference or not.
The result of ANOVA was continued using Tukey HSD test with 95% confidence level (α
= 0.05).
RESULT AND DISCUSSION Manufacture and evaluation of pectin
Pectin is successfully retrieved from skin of pomelo. Extraction yield was obtained of 9.79%. Pectin of pomelo skin was evaluated include organoleptic test, identification test, content of ash, lost on drying, equivalent weight and content of methoxyl.
Based on identification test, pectin was obtained meets the requirements on Pharmacopoeia Indonesia edition V.
Table 2. Result of evaluation pectin from pomelo skin
Test Result Standard Conclusion
Content of ash 2,39 % < 10% Meet the requirement
Lost on drying 7,79 % < 12% Meet the requirement
Equivalent weight 770,58 mg 600 – 800 mg Meet the requirement Content of methoxyl 7,43 % High :> 7,12%
Low : < 7,12% High methoxyl Table 3. Result of identification test of pectin
Identification Result Requirement
1. Stiff gel formed Stiff gel formed
2. Clear gel precipitate was formed Clear precipitate formed, such as gelatin
3. Semi gel formed Gel or semi gel formed
4. Colorless gel formed, agglomerated
and become when heated Precipaitate formed, such as gelatin, colorless and spread, become white and agglomerate when
heated Table 4. Result of organoleptic test DMP edible film
Formula Organoleptic test
Color Smell Sticky Taste
I Transparant yellowish Typical oleic acid No Sweet
II Transparant yellowish Typical oleic acid No Sweet
III Transparant yellowish Typical oleic acid No Sweet
IV Transparant yellowish Typical eugenol No Sweet
V Transparant yellowish Typical eugenol No Sweet
VI Transparant yellowish Typical eugenol No Sweet
46 Manufacture and evaluation of edible film
Difference type and concentration of plasticizer used have no effect against color, sticky and sweet taste. However, difference typical smell was produced attend plasticizer usage i.e. formula I to III have smell typical of oleic acid, whereas formula IV to VI have typical smell of eugenol.
Uniformity of weights
Deviation percent of weigh 20 edible film was collected, formula I to VI meets the requirements of weights uniformity with an average of 204-234 mg where no more than two edible films that deviate higher than 7.5% and not one edible films that deviate more than 15%.
Determination of film thickness
Thickness increases along with increasing concentration of plasticizer. Edible films thickness influenced by concentration of plasticizer were added. Edible film with eugenol has thickness of 0,25 mm i.e. highest. Whereas, edible film with oleic acid has thickness of 0,163 mm i.e. smallest. Concentration of oleic acid and eugenol will increase solution viscosity and edible film thickness. Barus (2002) concluded that increase of thickness caused by variation concentration of film forming, while solution is poured in the same volume.
Tensile strength and elongation
Tensile strength edible film eugenol, i.e.
31-38 kg/cm2, greater than edible film oleic acid that is 20-30 kg/cm2. Figure 1. shows the tensile strength edible film measurement chart. From the chart, an increase in concentration plasticizer caused a decrease in tensile strength, in accordance with general properties of plasticizer usage. It is caused by the low water binding ability of eugenol in between polymer chain so that water is separated from polymer chain and limit its ability to lower hydrogen bonding between polymer chains compared with oleic acid (Sitompul et Al. 2017). Based on statistical analysis, tensile strength data shows
that concentration interval 2% of oleic acid and eugenol as plasticizer produces significantly different tensile strength on DMP edible film.
Figure 1. Charts influence of oleic acid and eugenol concentration against tensile strength edible film
Tensile strength measurements are usually followed by elongation measurement.
Edible film eugenol has higher elongation i.e.
36-52% compared to edible film oleic acid that is 23-34%. Plasticizer usage tended to tensile strength decreases and elongation increases because plasticizer can reduce force between molecules and increase mobility chain biopolymers (McHugh and Krochta 1994).
Based on statistical analysis, data elongation show that concentrations interval 2% of oleic acid and eugenol produce significantly different elongation on DMP edible film.
Figure 2. Charts influence of oleic acid and eugenol concentration against elongation edible film
Disintegration Time
47 Addition of plasticizer improving strength of matrix film and not easily disintegrated in water. Concentration of oleic acid and eugenol getting high can slow disintegration time of edible film. Disintegration time of edible film 2% oleic acid is 1 min 12 secs whereas disintegration time of edible film 2% eugenol is 1 min 30 secs. Data results of disintegration time edible film ranges from 1-3 secs. Disintegration time edible film of oleic acid have destroyed faster than edible film of eugenol. This occurs because oleic acid is more water soluble than eugenol.
Determination of pH
Solution pH of edible film from sixth formula shows significant differences due to presence of interactions between materials with amount of plasticizer used. Oleic acid and eugenol have different structure but the pH produced almost same because ions H+ in oleic acid and eugenol is not much different from the average pH 6,22-6,29. pH testing is crucial for oral preparations because if pH is too high or low can irritate the mucosa of the mouth.
Determination and uniformity of content Maximum wavelength of DMP was measured using 40 ppm solution in pH 6.8 of medium phosphate as solvent using spectrophotometer UV-Vis generated at 277.7 nm with 0.2590 absorption. That number slightly different with literature in Jackson et al.
(1986) i.e. 278 nm.
Calibration curve was created with four variance concentration i.e. 30, 60, 90, and 120 ppm. Absorption value was 0,248; 0,467; 0,673;
and 0,881 respectively. A linear regression equation obtained that y = 0.0070 + 0, 041x with correlation coefficient value is 0.9999.
Percentage of DMP on edible films was obtained that 96.80%, 91.42%, 83.16%, 86.99%, 94.24% and 92.68% respectively. These result not meet requirement on Indonesian
Pharmacopoeia 5th Edition, where DMP contains not less than 98.0% and not more than 102.0%. This is can because at manufacture process any possibility the drug left on container or mold, so that the resulting percentage of content do not meet the requirements.
Uniformity of content test on edible film was done. This is done because dose of DMP is 5 mg in 250 mg dosage weight. On formula I, SBR value is 1.88% where meet requirement Indonesian Pharmacopoeia 5th Edition i.e. SBR value for uniformity of content is less than 2%.
Whereas on formula II – VI, SBR value exceeds requirements.
CONCLUSION
Based on results of research, characteristic edible film DMP of eugenol as plasticizer better than characteristics edible film DMP of oleic acid at concentration of 2%, 4%
and 6%.
ACKNOWLEDGEMENT
We would like to thank Lembaga Penelitian dan Pengembangan (Lemlitbang) from Universitas Prof. DR. Hamka for funding this research through the “skim penelitian pengembangan ipteks (PPI)” program.
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