FORMULATION AND PHYSICAL EVALUATION OF MICROEMULSION AND W/O/W MULTIPLE EMULSIONS DOSAGE FORMS WITH ALPHA ARBUTIN, LACTIC ACID, AND NIACINAMIDE AS SKIN-WHITENING COSMETICS

Objective: The present study aimed to formulate and determine the physical stability of microemulsion and W/O/W multiple emulsions, containingα arbutin, lactic acid, and niacinamide, as skin-whitening cosmetics.Methods: A skin lightening effect can also be obtained from lactic acid, which accelerates the turnover of pigmented cells in the epidermis, andfrom niacinamide, which inhibits the transfer of melanosomes from melanocytes to keratinocytes. These active ingredients were combined inmicroemulsion and W/O/W multiple emulsions dosage forms in various concentrations of Tween 80 as an emulsifier. An evaluation and physicalstability test were carried out during 12 weeks of storage at 28±2°C, 4±2°C, and 40±2°C, as well as a cycling test.Results: The results showed that a microemulsion could be prepared in 25-35% of Tween 80 (surfactant) and 10% of ethanol (co-surfactant), andthat it had globule sizes of 2.397-16.8 nm, a transparent, pseudoplastic flow, and was most stable in storage at 28±2°C. Microemulsion with 35% ofTween 80 was the most stable microemulsion formula because it had the smallest globule size, the most stable distribution profiles of globule sizes,and the highest viscosity. W/O/W multiple emulsions could formulated made with 2.5-4.5% of Tween 80 (external emulsifier) and 3% of Span 80(internal emulsifier); these emulsions had a pseudoplastic-thixotropic flow and were most stable in storage at 28±2°C.Conclusions: The formulation of multiple emulsions with 2.5% of Tween 80 was the most stable formula, with a stable distribution profile of globulesizes during 8 weeks of storage at temperatures of 28±2°C, 4±2°C, and 40±2°C

PREPARATION AND CHARACTERIZATION OF CHITOSAN SUCCINATE AS COATING POLYMER FOR ENTERIC-COATED TABLET

Objective: This present study was aimed to evaluate the potential of chitosan succinate as a coating polymer.Methods: In this study, chemical modification of chitosan was performed by substituting a succinate group into chitosan's amine group. This reactionused a water-solvent method to obtain chitosan succinate. Chitosan succinate was characterized and used as a coating agent in enteric-coated tabletdosage forms containing sodium diclofenac as the drug model at concentrations of 3% and 4% and combined it with hydroxypropyl methylcellulosephthalate (HPMCP) in ratios of 3:1 and 2:1 (3%). The obtained tablets were evaluated based on their physical appearance, uniformity of weight andsize, thickness film, disintegration time for an hour in acid, and dissolution profile.Results: Although the enteric-coated tablets with 3% and 4% chitosan succinate dissolved after 1 h in acid, they could not hold drug release in theacid medium under 10%. The enteric-coated tablet combined with chitosan succinate and HPMCP (3:1 and 2:1) at 3% did not dissolve after 1 h in theacid medium and could hold drug release up to 8.53% in acid.Conclusion: A combination of chitosan succinate and HPMCP (3:1 and 2:1) at 3% has a better ability to hold drug release in acid medium and met therequirement as a coating in enteric-coated tablet dosage forms

OPTIMIZATION OF SODIUM DEOXYCHOLATE-BASED TRANSFERSOMES FOR PERCUTANEOUS DELIVERY OF PEPTIDES AND PROTEINS

Objective: This study aims to formulate and characterize the transfersomes for percutaneous delivery of peptides and proteins. In particular, this study was a preliminary study for the transfersomes formulation of recombinant human epidermal growth factor (rhEGF) for topical delivery. Methods: The transfersomes was prepared by thin film hydration method using phosphatidylcholine and sodium deoxycholate as vesicle former. In this study, transfersomes formulas were optimized, namely TF1, TF2, TF3, and TF4 with several ratios of phospholipid and surfactant which were 90:10, 85:15, 80:20, and 75:25, respectively. Afterward, the transfersomes were characterized in terms of particle size distribution, polydispersity index, zeta potential, morphology of vesicles, and deformability index. Results: The results showed that the best formulation was TF3 with the ratio of 80:20 with a particle size of 118.6±1.33 nm, polydispersity index of 0.102±0.011, zeta potential of-30.9±0,46 mV, and deformability index of 1.182±0.08. TEM analysis also showed spherical and unilamellar vesicles of transfersomes. Conclusion: This work demonstrated that the sodium deoxycholate-based transfersomes could be potential to be further formulated with peptide and protein for percutaneous delivery

FORMULATION OF AN ANTI-WRINKLE HYDROGEL FACE MASK CONTAINING ETHANOL EXTRACT OF NONI FRUIT (MORINDA CITRIFOLIA L) FOR USE AS A NUTRACOSMECEUTICAL PRODUCT

Objectives: Noni fruit (Morinda citrifolia L) containing ursolic acid and 3,3' bisdemethylpinoresinol can be useful as an anti-wrinkle agent. Thehydrogel face mask is an alternative skin care product.Methods: In this study, 0.1% ethanol extract of noni fruit was formulated with a concentration of 4% sodium alginate and 0.5% xanthan gum to formthe hydrogel face mask. Physical stability of the hydrogel face mask was evaluated using organoleptic observation, consistency rates, swelling indexmeasurements, and mechanical strength.Results: The results showed that the hydrogel face mask has good water holding capacity, a tensile strength of 35.6524±0.8842 kgf/cm2, an elongationrate of 272.00±4.47%, and remains stable in color and odor for 12 weeks.Conclusions: This study revealed that the hydrogel face mask containing an ethanol extract of noni fruit is stable and has good physical characteristics;therefore, the hydrogel face mask is satisfactory for use as a nutracosmeceutical product

FAST-DISINTEGRATING TABLET FORMULATION OF GINGER (ZINGIBER OFFICINALE ROSC.) EXTRACT USING COPROCESSED EXCIPIENT OF PRE-GELATINIZED CASSAVA STARCH-ACACIA GUM

Objective: Fast-disintegrating tablets (FDTs) are tablets that disintegrate and/or dissolve rapidly in the mouth, thereby helping patients who havedifficulty in swallowing tablets. Ginger extract contains gingerol and is generally known for its antiemetic property. This study aimed to obtain anduse coprocessed excipients of pre-gelatinized cassava starch (PCS) with acacia gum (AG) in FDT formulations of ginger extract.Materials and Methods: In this research, five types of PCS-AG coprocessed excipients (Co-PCS-AG) were prepared by mixed PCS and AG with thefollowing ratios mass of PCS and AG were 5:5, 6:4, 7:3, 8:2, and 9:1. The prepared Co-PCS-AG excipients were characterized in terms of morphology,particle size distribution, moisture content, pH, flow-ability properties, and swelling index. Based on the results, three types of Co-PCS-AG excipients,which were 7:3, 8:2, and 9:1, were selected for use in FDT formulation of ginger extract. The FDTs were then examined for tablet hardness, tabletfriability, wetting time, and disintegration time.Results: The results indicated that Co-PCS-AG 9:1 was ideal excipient to be used in FDT formulation, as it revealed good flow properties and swellingindex compare to the other ratios. The Co-PCS-AG excipients were formulated into tablets and evaluated. Analysis of the ginger extract FDTs revealedthat the FDT prepared using Co-PCS-AG 9:1 excipient had the best performance with tablet hardness, friability, wetting time, and disintegration timeof 0.7 kp, 2.12%, 93 seconds, and 134 seconds, respectively.Conclusions: Co-PCS-AG 9:1 excipient is a potential excipient with ideal binder, disintegrant, and filler properties for use in FDT formulation

FORMULATION OF DICLOFENAC SODIUM SUSTAINED RELEASE TABLET USING COPROCESSED EXCIPIENTS OF CROSSLINKED AMYLOSE–XANTHAN GUM AS MATRIX

Objective: This present study was intended to design sustained release tablet containing diclofenac sodium using a matrix of excipient co-processed xanthan gum-crosslinked amylose.Methods: In the previous study, xanthan gum and amylose have been physically and chemically modified by the co-processed and crosslinking method, resulting co-processed excipient xanthan gum-crosslinked amylose are Co-CLA6-XG and Co-CLA12-XG (method A); CL6-Co-A-XG and CL12-Co-A-XG (method B) with each ratio 1:1, 1:2 and 2:1. All excipients had a good swelling index, high viscosity and good gel strength, good characteristics to be used as a matrix for sustained release tablet dosage form. In this study, a tablet with excipient Co-CLA6-XG, Co-CLA12-XG, CL6-Co-A-XG and CL12-Co-A-XG were formulated by direct compression method. The prepared formulations were evaluated for weight variation, thickness, and diameter, hardness, friability, drug content estimation, swelling index, in vitro drug release are within the acceptable standard.Results: The release profile of diclofenac sodium which contained matrix from Co-CLA6-XG (F1–F3), Co-CLA12-XG (F4–F6), CL6-Co-A-XG (F7–F9) and CL12-Co-A-XG (F10–F12) in phospate buffer medium for 8 h, showed that the sustained release profile followed zero order kinetics (F1–F6, F9, F11) and Korsmeyer-Peppas (F7, F8, F10, F12). Formula F1 to F6 tablet formulations could be applied as sustained release tablet formula and could retard drug release up to 16 h. Then, formula F7 to F12 could be applied as sustained release tablet formula and could retard drug release up to 32 h.Conclusion: It may be concluded that coprocessed excipients of crosslinked amylose–xanthan gum can be used for the preparation of sustained release tablets of diclofenac sodium and can retard the drug release for 16 h and 32 h.Keywords: Excipient coprocessed xanthan gum-crosslinked amylose, Matrix, Diclofenac sodium, Sustained release table

DEVELOPMENT OF MICROEMULSION AND WATER/OIL/WATER MULTIPLE EMULSION CONTAINING BETA-ARBUTIN, LACTIC ACID, AND SODIUM ASCORBYL PHOSPHATE

Objective: In addition to lactic acid and sodium ascorbyl phosphate, which have whitening effects, beta-arbutin is a safe whitening agent for skin.Combining these three substances should reduce the concentration of each one in a formula and achieve an optimal whitening effect. In this study,microemulsions and water/oil/water (W/O/W) multiple emulsions were applied to produce a formula containing these whitening agents.Methods: All the active ingredients were formulated into microemulsions and W/O/W multiple emulsions with different concentrations of Tween 80and Span 80 as emulsifiers to obtain a stable formula. Twelve-week physical stability studies were performed for every formula at low (4±2°C), room(28±2°C), and high (40±2°C) temperatures.Results: The produced microemulsions were transparent with a mean droplet size of 15.50 nm. In addition, the W/O/W multiple emulsions containeddroplets within droplets, which were dispersed in a continuous phase with an inner droplet size of 0.15 μm and an outer droplet size of 0.37 μm. TheW/O/W multiple emulsions showed pseudoplastic thixotropic flow properties. Furthermore, the microemulsions were stable at low (4±2°C) androom (28±2°C) temperatures, while the W/O/W multiple emulsions were stable at room (28±2°C) and high (40±2°C) temperatures.Conclusion: It was concluded that the combination of beta-arbutin, lactic acid, and sodium ascorbyl phosphate was suitable for formulating intomicroemulsions as well as W/O/W multiple emulsions as whitening cosmetic products

DEVELOPMENT OF COPROCESSED EXCIPIENTS OF XANTHAN GUM AND ACACIA GUM AS A CONTROLLED RELEASE MATRIX FOR FAMOTIDINE FLOATING TABLETS

Objective: Controlled release floating tablets require excipients, which act as a matrix to control the release of the active drug and facilitatethe tablet floating in the gastric milieu. One potential excipient is coprocessed excipients of xanthan gum and acacia gum (Co-XG-GA), which isa physical modification of the two natural polymers. In this study, we produced several Co-XG-GA and used them as matrices in floating tabletformulations.Methods: Several coprocessed excipients were prepared from xanthan gum and acacia gum at ratios of 1:1, 1:2, 2:1, 1:3, and 3:1. The obtainedexcipients were then characterized physically, chemically, and functionally. The coprocessed excipients were then formulated in floating tablets usingfamotidine as the drug model. The floating tablets were then evaluated in terms of the tablet floating capabilities and the drug release in HCl mediumat pH 1.2 for 8 h.Results: Our results showed that the coprocessed excipients were a fine powder, odorless, and a grayish-white color. The excipients had a goodswelling index, fairly large viscosity, and good gel strength; hence, they were suitable to be applied as the matrices of floating tablet formulations. Thefloating tablets of F2, which contained the Co-XG-GA 1:2, demonstrated the best characteristics with 8.33±0.58 min of floating lag time and 24 h oftotal floating time. Further release studies revealed that the famotidine floating tablets, which used Co-XG-GA (F1–F5) as matrices, controlled drugrelease with zero-order release kinetics and could be used for controlled release dosage forms.Conclusion: Collectively, our results indicate that the Co-XG-GA can be applied as matrices in controlled release floating tablet

FORMULATION OF MULBERRY LEAF (MORUS ALBA L.) EXTRACT HYDROGEL BEADS USING CROSS-LINKED PECTIN

Objective: Nutraceutical products have now gained considerable interest to be consumed regularly. Since the active substances in nutraceuticalproducts are provided by nature, they are safe to consume. The development of a dosage form and the appearance of a modern nutraceutical productcan improve product quality. Therefore, this research aimed to formulate a nutraceutical product, mulberry leaf extract, into hydrogel beads that swellin water and that can be administered orally.Methods: Deoxynojirimycin, the active substance in mulberry leaf extract hydrogel beads, has the efficacy of an anti-diabetic agent. In this research,there were four formulations: The variations 1:2 and 1:3 of the extract-to-polymer ratio and the variations 2.5% and 5% of the cross-linkerconcentration.Results: The results showed that hydrogel beads had a spherical form with an unsmooth surface and a brown color, and they were able to swell inwater. The best formula was Formula 1, with a 1:2 extract-to-polymer ratio and a 2.5% cross-linker concentration. Formula 1 produced an averagediameter of 3.6 mm, a swelling ability of 210.68%, and immediate swelling in water for 30 seconds.Conclusions: Mulberry leaf extract hydrogel beads could be used as an interesting nutraceutical product

Optimization of PVA-Arabic Gum–Honey-based Electrospun Nanofibers as Candidate Carrier for Peptide and Protein Delivery

Nanofibers dressing exhibit several advantageous characteristics for accelerating wound healing, such as its similar structure to the extracellular matrix (ECM), high surface area/volume ratio, high porosity and high loading capacity of drug. The nanofibers dressing which were prepared by the electrospinning technique using combination of synthetic and natural polymer excipients capable of fulfilling the ideal wound dressing criteria. This study aimed to develop nanofibers dressing prepared from polyvinyl alcohol (PVA), Arabic gum (GA) and honey by electrospinning method. This study focused on the effect of electrospinning parameters and the morphology of electrospun nanofibers of the blended solutions made from PVA (9% w/v) – GA (1% w/v) and honey (at varied concentrations of 0;1;3% w/v) with or without Triton X-100 (0.05% v/v). The effect of varied process parameters such as voltage and flow rate in electrospinning was also investigated. The blended solutions with the various concentration of honey at 0;1;3% w/v and Triton X-100 were named as FAt, FBt, and FCt, respectively, while the blended solutions without Triton X-100, were named as FA, FB, and FC. The optimum electrospining parameter were 18 KV and 5 µl/minute for FAt, FBt, and FCt; and 20 KV and 10 µl/minute for FA, FB, and FC. Electrospun nanofibers of FAt, FBt, FCt showed smoother and more uniform fibers in comparison to the nanofibers FA, FB, and FC. The average nanofibers diameter of FAt, FBt, FCt were 244±45; 266±45; 283±57 nm, respectively, while the average nanofibers diameter of FA, FB, FC was 406±140, 457±168, 594±204 nm, respectively. Higher concentration of honey increased the diameters of nanofibers. The average nanofibers diameter of FAt, FBt, and FCt were within nanoscale in range of the ECM (50-500 nm), which were suitable for accelerating wound healing. Therefore, this study indicated that PVA-GA-honey nanofibers dressing is suitable to be further developed as carrier for growth factors