NICOTINAMIDE MICROEMULSION-BASED GELS 403 60°C for 2 days and observed for color change. Indeed, only the color of soybean oil was darker. The result can be explained by the degradation of soybean oil via lipid oxidation, which was catalyzed by high temperature like other natural oils such as coconut oil (25). Although MBG-2 and MBG-3 were physically stable like MBG-1, their appearance was unsatisfactory. Therefore, only MBG-1 was selected to be analyzed with HPLC for the chemical stability study. The content of nicotinamide compared to the initial concentra- tion after 2 months storage was found to be 99.98% when stored at 4°C and 98.18% when stored at ambient temperature. Nicotinamide was entrapped in the internal phase of the MBGs therefore, it was protected from degradation. It was reported that ascorbyl palmitate was more stable in w/o than in oil-in-water (o/w) MEs composed of identical components since its cyclic ring, oxidation sensitive group, was shielded in the internal aqueous phase (10). IN VITRO RELEASE OF NICOTINAMIDE FROM THE STUDIED FORMULATIONS Because of its good appearance and stability, MBG-1 was selected to study for in vitro release. Figure 2 shows the in vitro release profi les of nicotinamide from MBG-1 with three different mathematical models, i.e., zero order, fi rst order, and Higuchi. The best linearity with the r2 value of 0.9932 was found in zero order model during the studied period. Hence, the ability of MBG-1 to deliver nicotinamide was independent of the concentration of the active compound.. The release rates of nicotinamide from MBG-1, ME, and CC calculated as percent of the initial concentration per hour are shown in Table II. The release of nicotinamide tended to be in the rank order of from MBG-1 ME CC. Figure 2. In vitro release profi les of nicotinamide from MBG-1 with different mathematical models, i.e., zero order, fi rst order, and Higuchi.
JOURNAL OF COSMETIC SCIENCE 404 Although C C is o/w formulation and nicotinamide locates in the outer phase, it provided the lowest release rate of nicotinamide. It was found that the viscosity value of CC (6827.87±549.63 cP) was much higher than that of MBG-1 and ME. Release ability was reported to be inversely related to the viscosity of the continuous phase (26). Moreover, the complex partition of nicotinamide among all the compositions may limit the trans- ferring of nicotinamide through the membrane (27). ME increased the release rate of nicotinamide when compared with CC. The possible mechanisms of ME in enhancing nicotinamide release were that the thermodynamic ac- tivity of nicotinamide in the ME could be modifi ed to favor partitioning into the mem- brane and that the nanosized droplets dispersed in the continuous phase of the ME could move easily and carry nicotinamide through the membrane (7). MBG-1 exhibited the highest release rate. The structure of colloidal silica is amorphous and composed of submicron-sized spheres, which are 40–60% fused into short chains, very highly branched, 0.1–0.2 microns long. Hence, the formation of three-dimensional networks of particles created the mobility of the network chains in the gel contributing to the loose structure of the matrix, resulting in nicotinamide burn out (28,29). Low af- fi nity between hydrophilic nicotinamide and hydrophobic phase subsequently increased the release of nicotinamide. As expected, the 3% w/w nicotinamide aqueous solution provided cumulative amount active released markedly higher than MBG-1 (data not shown). However, the aqueous solution was not an appropriate vehicle for topical delivery of any active compound be- cause of the lipophilic nature of the stratum corneum. The release rate of nicotinamide from the aqueous solution drastically increased during 0.5 to 12 h and reached a plateau state after 12 h. The release profi le of MBG-1 did not show a plateau state since MBG-1 acted as active compound reservoirs (30). CONCLUSIONS It was observed that the order of clarity and viscosity in prepared nicotinamide MBGs was MBG-1 MBG-3 MBG-2. All samples were physically stable at 4°C and ambient temperature (approximately 30°C) during the 2 months of storage a darker color devel- oped when stored at 60°C. Since MBG-1 was desirable according to its appearance and viscosity, it was further analyzed for residual nicotinamide content by HPLC. It was found that MBG-1 was chemically stable. The remaining nicotinamide in MBG-1 after storage at 4°C and ambient temperature for 2 months was 99.98% and 98.18%, respec- tively. In vitro release kinetics of nicotinamide from MBG-1 was best fi tted to zero order model. The rank order of release rate of nicotinamide from different formulations was Table II Release Rates of Nicotinamide from Different Formulations Sample Release rate (percent of initial concentration/hour) MBG-1 0.30716 ME 0.00029 CC 0.00019
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