Synthesis and Characterization of Modified Sago Starch Films for Drug Delivery Application

Transcription

1 AUSTRALIAN JOURNAL OF BASIC AND APPLIED SCIENCES ISSN: EISSN: Journal home page: Synthesis and Characterization of Modified Sago Starch Films for Drug Delivery Application Shabirah Ezan, Sumaiya Zainal Abidin, Fatmawati Adam Faculty of Chemical and Natural Resources Engineering, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia. Address For Correspondence: Fatmawati Adam. Faculty of Chemical and Natural Resources Engineering, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia. Tel: ; A R T I C L E I N F O Article history: Received 18 September 2016 Accepted 21 January 2017 Available online 26 January 2017 Keywords: Edible Film; Modified Sago Starch; Vegetable Capsule A B S T R A C T Starch has gained an attention as a potential gelatin substitute for vegetarian hard capsule production for drug delivery application due to its abundant, cheaper price and good film forming properties. Modified sago starch has been used for the film and capsule production in this study instead of native starch because it tends to has drawbacks when compared to gelatin. Furthermore, modification of the starch structure can improve the starch properties. In this work, the capsule was produced by using 25 w/w% modified sago starch (MSS) solution with the addition of additives (semi-refined carrageenan and titanium dioxide) and glycerol as a plasticizer. The addition of some additive such as carrageenan and titanium dioxide was expected to help the stability of film for capsule making. Characterization of the capsule s film has been carried out by analyzing the spectrum of Fourier transform infrared (FTIR), the thermograms of differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), and the scanning electron microscopy (SEM) morphology. Although there was no significant difference spotted with the addition of semi-refined carrageenan and titanium dioxide in the FTIR results, DSC and TGA thermograms show that there was a slight decrease in thermal stability and resistance by adding semi-refined carrageenan and titanium dioxide. This portrays the stability of MSS alone without the need of the additives. Meanwhile, the morphology illustrates that with the addition of semi-refined carrageenan and titanium dioxide, some roughness were found on the surfaces of the film. Interestingly, the addition of semi-refined carrageenan and titanium dioxide improved the water composition of the film which capable to control the film brittleness. INTRODUCTION Gelatin has been used to produce pharmaceutical capsules since early 19th century and still dominates the pharmaceutical capsule materials. However, the higher price of the raw materials and well-recognized shortcomings of gelatin capsules, such as animal-derived ingredients and the instability of moisture in gelatin, have led to attempts to use replacement substances from plant material, such as from polysaccharide (Jones, 2004). As reported by Karki et al., (2016), the polysaccharide such as starch-based hydrophilic films could be used for controlled drug delivery. Starch displays promising properties for edible film production because of its superior molding and film-forming properties, high oxygen barrier, and great mechanical strength (Bae et al., 2008). Starch also can be categorized as a natural polymer and it is commonly used as a thickening agent for pharmaceutical excipient because it is widely available, inexpensive, and biocompatible and can be modified in various ways. Modified starch such as carboxymethyl starch is reported to have a great importance in pharmacy, medicine, cosmetics, food industry, environmental protection and many other industrial applications as Open Access Journal Published BY AENSI Publication 2017 AENSI Publisher All rights reserved This work is licensed under the Creative Commons Attribution International License (CC BY). To Cite This Article: Shabirah Ezan, Sumaiya Zainal Abidin, Fatmawati Adam., Synthesis and Characterization of Modified Sago Starch Films for Drug Delivery Application. Aust. J. Basic & Appl. Sci., 11(3): , 2017

2 177 Shabirah Ezan et al, 2017 described by Wilpiszewska et al., (2015). Contrasting with the native starch, carboxymethyl starch is soluble in cold water and does not exhibit a tendency to retrogradation or recrystallization. Moreover, its good freeze thaw characteristics indicate stability during storage at low temperature (Noor Fadzlina et al., 2005). Nevertheless, modification may cause adverse influence on the functional properties despite it claims to improve the starch properties (Fakharian et al., 2015). The problem can be solved by combining with other biopolymers and additives in which the modified starch properties may be improved (Lafargue et al., 2007 and Zhang et al., 2015). The main aim of this work is to synthesize the capsule film from MSS in the addition of semi-refined carrageenan and titanium dioxide. The films were evaluated on the stability and morphology properties. MATERIALS AND METHODS Materials: Modified sago starch (carboxymethyl sago starch) used in this work was purchased from My Synergy Factors (M) Sdn Bhd, Malaysia. Semi-refined carrageenan (sc) was procured from Tacara Sdn Bhd, Sabah, Malaysia. Titanium dioxide and glycerol (plasticizer) used was obtained from Sigma Aldrich and Merck, Malaysia. Film preparation: The film solutions preparation was referred to the method conducted by Bae et al. (2008). The amount of glycerol (15 % w/w starch) was weighed and dissolved in distilled water at a 50 C temperature for 30 minutes. Modified sago starch (MSS) (25 % w/w) or S1 was dispersed in the aqueous glycerol solution. The solution was mixed at 50 to 90 C with 2 hours time interval. The final mixture was degassed to remove bubbles. The film solution was molded onto a stainless-steel plate and then dried overnight at 32.5 C. The dry film was peeled, cut into test specimens, placed in a box containing silica gel, and stored at a room temperature until use for testing. The experiment was repeated with the addition of 1 % w/w semi-refined carrageenan (sc), the solution was stirred for 1 hour before adding MSS (25 % w/w + sc) or S2 and the addition of 1 % w/w sc with 1 % w/w titanium dioxide (TiO 2), stirred for 1 hour before adding MSS (25 % w/w + sc + TiO 2) or S3. Film Characterization: The FTIR spectra of sample film were recorded on Perkin Elmer Spectrum 100 spectrometer (PerkinElmer, MA, USA) in the range of cm -1. Differential scanning calorimetry (DSC) analysis was performed by using TA/Q1000 series (TA Instruments, New Castle, DE, USA) in a nitrogen atmosphere between 50 C and 170 C with a heating rate of 10 C/min. The sample were prepared at sample weight of ~5mg and hermetically sealed. Thermogravimetric analysis (TGA) was performed by using TA instrument (TA Instruments, New Castle, DE, USA) in a nitrogen atmosphere between 100 C and 500 C with a heating rate of 10 C/min. Scanning electron microscopy method was used (Carl Zeiss EVO50, Zeiss, Oberkochen, Germany) to analyze the morphology of the capsule film. To eliminate the moisture, the film was stored in desiccators for overnight prior to characterisation. RESULTS AND DISCUSSION Fourier Transform Infrared Analysis (FTIR): FTIR spectroscopy was used to examine the functional group of the capsule films to indicate any potential physical interactions. The FTIR spectra of the films can be seen in Fig. 1. There were not much peak differences shown for all the films with the addition of semi-refined carrageenan and TiO 2. The FTIR spectrum of the S1 film shows the typical peaks of sago starch with the addition of new peaks due to the carboxymethylation reaction (Basri et al., 2016). The S1 film absorption peak showed the O-H stretching at 3348 cm 1.The absorption peaks at 2935 cm 1 and 1586 cm 1 show the C-H stretching and tightly bound water present in the starch molecule. Absorption peaks at 1406 cm 1 and 1308 cm 1 indicates the substitution of CH 2COO Na + group on the starch molecular chain through carboxymethylation. In general, the peaks patterns for all the sample films were identical with some slight differences. This was due to the carrageenan effect on the solid-state behavior of the blends that was unseen, regardless of the firm carrageenan influence on the rheological behavior in the solution and in the gel state (Lafargue et al., 2007). According to Mohd Daud et al. (2015), supposedly the spectra bands present for the commercial semi-refined carrageenan were cm -1, cm -1, cm -1 and cm -1 respectively where it indicates the presence of indicated the presence of C O SO 3 on D-galactose-4-sulphate, C O of 3,6-anhydro-D-galactose, glycosidic linkage (C O) of 3,6-anhydro-D-galactose and S=O stretching of sulphate esters. This explanation also applicable to the addition of TiO 2. TiO 2 was also believed to only act as an opacifying agent (Vilivalam et al., 2000). The spectra band for TiO 2 is in the range of cm -1.

3 Heat flow (w/g) Transmittance (%) 178 Shabirah Ezan et al, 2017 S1 S2 S Wavenumber (cm -1 ) Fig. 1: FTIR spectra of S1 film, S2 film and S3 film Differential Scanning Calorimetry (DSC): DSC thermal profile of the plasticized films with the addition of semi-refined carrageenan and TiO 2 were shown in Fig. 2. The transition temperatures of S2 and S3 related to gelatinization were considerably smaller than S1 film. The results showed that the endothermic peak for S1 at temperature ºC. Meanwhile, the endothermic peak for S2 was at temperature 79.9ºC and for S3 was at 93.4ºC. As reported by Bigi et al. (2002) and Gladkowska-Balewicz et al. (2014), the addition of an additive may improve the thermal stability. Nevertheless, clear shifted of endothermic peak to lower peak can be seen with the additional of the additives (semi-refined carrageenan and TiO 2) which may indicate slight decreased of thermal stability. The graph exhibits a broad gelatinization curve for all film samples especially with the addition of semirefined carrageenan and TiO 2. The graph displays a broad gelatinization curve for all film samples possibly because the number of hydrogen bonds needs to be broken for the swelling of starch granules was reduced. As previously reported by Noor Fadzlina et al. (2005), the presence of bulky groups in the starch chain seems to have a weakening effect on the granular structure of starch where it interferes the intermolecular and intramolecular hydrogen bonding. In addition, carboxymethyl group possesses a hydrophilic characteristic which supports the starch granules hydration easily and hence helps to reduce the MSS capsule films gelatinization temperature. 2.5 S1 S2 S Temperature (ºC) Fig. 2: DSC thermograms of S1 film, S2 film and S3 film

4 Weight (%) 179 Shabirah Ezan et al, 2017 Thermogravimetry Analysis (TGA): TGA was done to assess the stability of the films and to determine how the interface between the semirefined carrageenan and TiO 2 mix with the MSS could influence the stability. Fig. 3 shows TGA curves with a similar trend where the addition of semi-refined carrageenan has higher weight loss. In accordance with Martins et al. (2012), the weight loss derivative curves of films exhibit three significant thermal measures. Thermal analyses show that films are steady up until 100 C for all the formulations. The curve of 100 to 150 C was caused by the water evaporation and chemisorbed water through hydrogen bonds. This was considered as the first stage. At this stage, the water composition of the capsule films for S2 and S3 has improved compared to S1. Water capable to control the brittleness of the capsule film. At temperature of 150 to 240 C (second stage) was due to the glycerol existence; where glycerol changes the polysaccharide films structure by forming new bond or increasing the number of existing bonds. Meanwhile, at 240 to 330 C (third stage) was correlated to decomposition of the polysaccharide. The percentage weight loss for S1 was 46.40%, S2 was 46.70% and S3 was 48.25%. It can be detected from the results that the addition of semi-refined carrageenan and TiO 2 significantly increase the thermal degradation rate of S2 and S3 films when comparing the weight percentage loss of the three films which is in conformity as reported by Sanyang et al., (2015). However, the addition of these additives had caused the thermal resistance of the capsule films to slightly decrease. This may due to the molecular interaction of the mixtures that had weakened the strong intermolecular bonds between starch molecules and therefore drops the thermal resistance of the capsule films. This indicates that the thermal stability of the capsules decrease by adding the additives although the water composition of the capsule films was improved. 100 S1 S2 S Temperature (º) Fig. 3: TGA of S1 film, S2 film and S3 film Scanning Electron Microscopy Analysis (SEM): Fig. 4 shows the films surfaces for S1 film, S2 film and S3 film by using SEM. It can be seen from the figure that only S1 film that was smooth without any phase separation or heterogenous detected. Nevertheless, with the addition of semi-refined carrageenan and TiO 2, some roughness were demonstrated on the surfaces of the film. The addition of the semi-refined carrageenan and TiO 2 as an additive has increased the surface roughness where the film visual properties and appearance, as well as the film texture, has been affected. This indicates that starch, semi-refined carrageenan, and TiO 2 were three different phases that during the drying process, the ratios of shrinkage for the three materials were not the same (Zhang et al., 2013). However, the roughness may have been due to the inherent surface roughness of the additives itself. In this case, pre-treatment of the additives need to be done before mixing with other materials in producing the capsule film to overcome the problems. Another factor that might cause the uneven film surface can be due to the hydration temperature (Curtis-Fisk et al., 2012) or mixing phenomena that affecting the optical quality which need to be further study for the future work.

5 180 Shabirah Ezan et al, 2017 S1 S2 S3 Fig. 4: Films morphology of S1 film, S2 film and S3 film by using SEM Conclusion: From the data obtained, MSS shows a promise as a gelatin potential replacement to produce the hard capsule. In overall, the FTIR patterns for all the sample films were identical with only slight differences due to the carrageenan and TiO 2 effect on the solid-state behavior of the blends that was invisible. The clear shifted of DSC endothermic peak to lower peak with the additional of the additives may indicate slight thermal stability drop off. Similarly, for TGA thermograms, the addition of these additives had caused the thermal resistance of the capsule films to slight decrease due to the molecular interaction of the mixtures that had weakened the starch molecule intermolecular bonds. The addition of the additives also displays some roughness on the surfaces of the film; indicates that starch, semi-refined carrageenan, and TiO 2 were three different phases that during drying process, the ratios of shrinkage for the three materials were dissimilar. The obtained results provide an insight to improve the capsule films formulation based on the interactions between different type of polysaccharides to improve the capsule films properties when compared with other sources. The addition of semi-refined carrageenan and TiO 2 improved the water composition which can control the brittleness of the MSS film. The tensile strength study needs to be conducted to evaluate capsule film with the required tensile strength. ACKNOWLEDGEMENT We gratefully acknowledge Faculty of Chemical & Natural Resources Engineering, Universiti Malaysia Pahang and the research fund PGRS REFERENCES Bae, H.J., D.S. Cha, W.S. Whiteside and H.J. Park, Film and Pharmaceutical Hard Capsule Formation Properties of Mungbean, Waterchestnut, and Sweet Potato Starches. Food Chemistry, 106: Basri, S.N., N. Zainuddina, K. Hashim and N.A. Yusof, Preparation and Characterization of Irradiated Carboxymethyl Sago Starch-Acid Hydrogel and Its Application as Metal Scavenger Inaqueous Solution. Carbohydrate Polymer, 138: Bigi, A., G. Cojazzi, S. Panzavolta, N. Noveri and K. Rubini, Stabilization of Gelatin Films by Crosslinking with Genipin. Biomaterials, 23: Curtis-Fisk, J., J. Sheskey, K. Balwinski, K. Coppens, C. Mohler and J. Zhao, Effect of Formulation Conditions on Hypromellose Performance Properties in Films Used for Capsules and Tablet Coatings. American Association of Pharmaceutical Scientists, 13:

6 181 Shabirah Ezan et al, 2017 Fakharian, M-H., N. Tamimia, H. Abbaspourb, A.M. Nafchia and A.A. Karim, Effects of k- Carrageenan on Rheological Properties of Dually Modified Sago Starch: Towards Finding Gelatin Alternative for Hard Capsules. Carbohydrate Polymers, 132: Farhat, I.A., J.M.V. Blanshard and J.R. Mitchell, The Retrogradation Of Waxy Maize Starch Extrudates: Effects of Storage Temperature and Water Content. Biopolymers, 53: Gladkowska-Balewicz, I., I.T. Norton and I.E. Hamilton, Effect of Process Conditions, And Component Concentrations on The Viscosity Of K-Carrageenan and Pregelatinised Cross-Linked Waxy Maize Starch Mixed Fluid Gels. Food Hydrocolloids, 42: Jones, B.E., The Manufacture and Properties of Two-Piece Hard Capsules. In F. Podczeck, & B. E. Jones (Eds.), Pharmaceutical Capsules (pp ). London: Pharmaceutical Press. Karki, S., H. Kim, S-J. Na, D. Shin, K. Jo and J. Lee, Thin Films as An Emerging Platform for Drug Delivery. Asian Journal of Pharmaceutical Sciences, 11: Lafargue, D., D. Lourdin and J-L. Doublier, Film-Forming Properties of a Modified Starch/K- Carrageenan Mixture in Relation to Its Rheological Behaviour. Carbohydrate Polymers, 70: Martins, J.T., M.A. Cerqueira, A.I. Bourbon, A.C. Pinheiro, B.W.S. Souza and A.A. Vicente, Synergistic Effects Between K-Carrageenan and Locust Bean Gum on Physicochemical Properties of Edible Films Made Thereof. Food Hydrocolloids, 29: Mohd Daud, J., N.S. Warzukni, R. Mohd Salim and A.M. Zuberdi, Semi-refined k-carrageenan: Part 1. Chemical Modification of Semi-Refined k-carrageenan via Graft Copolymerization Method, Optimization Process and Characterization of its Superabsorbent Hydrogel. Oriental Journal of Chemistry, 31: Noor Fadzlina, Z.A., A.A. Karim and T.T. Teng, Physicochemical Properties of Carboxymethylated Sago (Metroxylon sagu) Starch. Food Chemistry and Toxicology, 70: Sanyang, M.L., S.M. Sapuan, M. Jawaid, M.R. Ishak and J. Sahari, Effect of Plasticizer Type and Concentration on Tensile, Thermal and Barrier Properties of Biodegradable Films Based on Sugar Palm (Arenga Pinnata) Starch. Polymers, 7: Vilivalam, V.D., L. Illumand and K. Iqbal, Starch Capsules: An Alternative System for Oral Drug Delivery. Research Focus: Review, 3: Wilpiszewska, K., A.K. Antosik and T. Spychaj, Novel Hydrophilic Carboxymethyl Starch/Montmorillonite Nanocomposite Films. Carbohydrate Polymers, 128: Zhang, L., Y. Wang, H. Liu, L. Yua, X. Liu, L. Chen and N. Zhang, Developing Hydroxypropyl Methylcellulose/Hydroxypropyl Starch Blends for Use as Capsule Materials. Carbohydrate Polymers, 98: Zhang, N., H. Liu, L. Yua, X. Liu, L. Zhang, L. Chena and R. Shanks, Developing Gelatin Starch Blends for Use as Capsule Materials. Carbohydrates Polymer, 92: