Key Engineering Materials Vol. 819

Abstract: Although caffeine was suggested as one of the pharmacological agents for the cellulite treatment, its skin permeation restricted. The present work was aimed at formulating caffeine loaded nanostructured lipid carriers (CAF-NLCs) containing coconut oil as a topical delivery system. CAF-NLCs were prepared by the ultrasonic emulsification method, using coconut oil as a liquid lipid. The proper selection of solid lipid and surfactants for these formulations were investigated. Subsequently, physicochemical properties, entrapment efficacy, stability, and in vitro drug release were evaluated. The CAF-NLCs containing coconut oil was successfully prepared using glyceryl behenate as a solid lipid and showed an interesting entrapment efficiency (62-99%). The obtained CAF-NLCs presented the nanosized range (≈ 60-390 nm), with a low polydispersity index and high negative zeta potential values (over ‐30 mV). However, the type and concentration of surfactant also affected these properties. These results suggested that CAF-NLCs containing coconut oil are the promising carrier for delivery of caffeine following topical application.

Abstract: Designing lauric acid (L) solvent-exchange induced in situ forming gel (ISG) was conducted in this study by using mixed solvents (N-methyl pyrrolidone (NMP), 2-pyrrolidone (PYR) and dimethyl sulfoxide (DMSO) at different ratios. The pH, density, viscosity, matrix formation, contact angle/surface tension and antimicrobial activities of 50% w/w L in mixed solvents were determined. The pH and density of solvent decreased apparently with L addition. More amount of PYR in the solvent mixture increased the density and viscosity. High viscous manner of PYR resulted in the high surface tension and contact angle. The solvent mixture of NMP/PYR promoted a higher contact angle than the other mixed solvent systems. L in DMSO, PYR or solvent mixture with high ratio of DMSO or PYR transformed into matrix-like rapidly while those in NMP or high ratio of NMP had slower matrix formation after exposure to aqueous fluid. NMP and PYR showed antimicrobial activities effectively against all test microbes while L matrix retarded their activities. The mixed solvent concept is interesting to use for designing ISG comprising L as matrix former to prolong the drug release.

Abstract: Alpha-mangostin (aMG) phase inversion induced in situ forming gel (ISG) was prepared by dissolving matrix formers including palmitic acid (P) and lauric acid (L) in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP). The pH and density values were in range of 4.42-6.22 and 0.9731-1.0943 g.cm^-3, respectively. The prepared formulas have low viscosity and high injectability which were suitable for injection. The gel formation behavior was affected by type of fatty acid and solvent. P dissolved in DMSO showed a rapid transformation into matrix at initial time. The extended release of aMG was attained in P-based ISG. aMG phase inversion induced ISG improved microbial inhibition.

Abstract: Water resistance of lauric acid (L) dissolved in biocompatible solvents mainly depended on the water affinity of solvent. L in DMSO (DL) was most sensitive to water and higher than L in N-methyl pyrrolidone (NL) and L in 2-pyrolidone (PL), respectively. From scanning electron microscope, differential scanning calorimetry, thermogravimetric analysis, powder x-ray diffractometry and hot stage microscope tests revealed the alteration of L crystal owing to the interference by solvent during precipitation. All L precipitates had lower melting point and degradation temperature than intact L in which L precipitated from 2-pyrrolidone exhibited the lowest melting temperature. These characteristics will be useful for modifying L in phase inversion in situ forming gel.

Abstract: Abstract. The in situ forming gel (ISG) has been developed as a controlled drug delivery system to prolong drug release. This study aims to prepare ISG system based on gamboge resin (GB) as matrix former. The various amounts of GB dissolving in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) were used to obtain the ISG systems and evaluated for their pH, viscosity, injectability and matrix forming. The antimicrobial activities against three strains of Staphylococcus aureus including the Methicilin Resistant S. aureus (MRSA) and Porphyromonas gingivalis were conducted. GB ISG systems exhibited good injectability with low viscosity. GB in DMSO showed a faster transformation to solid matrix compared to that in NMP. The gambogic acid (GA) content in crude GB was 33.70 ± 0.13%. The sustainable GA release from GB ISG could be attained. Thus, GB ISG exhibits the potential application as a drug delivery system for active compounds and is enable for using as a therapeutic dosage form owing to its antimicrobial activity.

Abstract: In situ forming microparticle (ISM) is an injectable emulsion drug delivery system comprising drug loaded in polymeric solution as internal phase and oil combined with emulsifier as external phase. This emulsion transforms into microparticle after contact an aqueous environment by solvent exchange mechanism. This study developed ISM using internal phase comprising 5% w/w doxycycline hyclate (DH) loaded with various concentrations of beta-cyclodextrin (β-CD) using N-methyl-2-pyrrolidone (NMP) as a solvent and external phase containing olive oil combined with glyceryl monostearate (GMS). High concentrated β-CD solutions in NMP are used as the internal phase of ISM. Matrix forming behavior is evaluated for their particle size, transformation to microparticle, pH, rate of matrix formation, contact angle and surface tension. Each emulsion had similar pH values about 3.5-4.1 and transformed into microparticles (particle size about 60 μm) after contact with phosphate buffer pH 6.8. The particle sizes of each preparation decreased significantly after transformed into microparticles and the more microparticles were evident with time. The rate of matrix formation of ISM was apparent slower than its internal phase and was slower with time. Contact angle of ISM and its internal phase showed good wetting which the surface tension of 35% w/w β-CD ISM was 44.19 mN/m. The β-CD ISM exhibited as the potential delivery system for incorporation of active compounds.

Abstract: The aim of this work was to apply the simplex lattice design in the formulation development of lozenges containing Vernonia cinerea extract. The different ratios of three diluents; milk powder, xylitol, and inulin were investigated. The preformulation parameters of powder mixtures were evaluated. The compressed lozenges were evaluated for their weight variation, thickness, hardness, friability, and disintegration time. Results showed that the ratios of the three diluents affected the preformulation parameters. The angle of repose data revealed that all 12 powder mixtures had excellent flow property. The formulation containing milk powder had the highest values of Carr’s index and Hausner ratio, indicating the poor compressibility. While formulation containing inulin had the best compressibility. A formulation containing xylitol had the lowest moisture content. The compressed lozenges had a weight variation of less than 5%, a diameter of 1.5 mm, a thickness of 5-6 mm, and a hardness of 2-12 kP. The 8 of 12 formulations had friability of less than 1%. Use of milk powder provided the longest disintegration time. The desired properties of developed lozenge achieved when the medium amount of xylitol and inulin and low amount of milk powder were used. The optimal diluent ratio providing the weight variation not more than 5%, the hardness of 5-8 kP, friability not more than 1%, and disintegration time not more than 30 min was an equal weight ratio of milk powder, xylitol, and inulin.

Abstract: Orodispersible tablet (ODT) provides rapid disintegration in the oral cavity. ODT improves the efficacy of using medicines especially in term of compliance in a patient with dysphagia. The major challenge of ODT is a bitter taste of active pharmaceutical ingredient (API); they can lead the patients to refuse medication. This study focused on the developing of the orodispersible disc (ODD) with a taste masking property by preparation of API particle that was taste-masked by polymers. The co-precipitation technique was used for the taste masking. Acetaminophen (APAP) taste-masked particles prepared with different grades of crospovidone were investigated for the taste-masking property. Kollidon^® CL-SF exhibited the lowest drug release. An increasing amount of Kollidon^® CL-SF caused increasing of APAP release. Particles consisted of APAP:crospovidone at ratio 3:1 showed the lowest drug release. It was probably due to the complexation which was shown by the FT-IR and DSC. Taste-masked particles were compressed as ODD by a hydraulic press machine. The disintegrating time of ODD was at the range of 12.62-17.35 s. The dissolution of ODD was focused on the taste-masking zone (drug release in 1 min). The ODD with ratio 3:1 particle (APAP: Kollidon^® CL-SF) showed the highest taste-masking performance, the lowest drug release. All disc formulations completely released APAP after 30 min. Therefore, the preparation of ODD contains taste-masked particles was promising to improve patient compliance of bitter APIs.

Abstract: Clindamycin (CM) is the one of antibacterial drugs that can be used to treat acne vulgaris. The commercial products in form of solutions, creams, and gels cannot provide the exact amount of the drug and constant drug release. Transdermal patches present an attractive point for reducing this limitation and there is no commercial transdermal patch containing CM available in the market nowadays. The purposes of this study were to develop CM loaded transdermal patches for the treatment of acne and to investigate the physical properties and drug release profile of the CM from the transdermal patches. The transdermal patch was prepared using 10% HPMC. The types and concentrations of additives (glycerin, polyethylene glycol(PEG) or propylene glycol (PG)), were varied to improve the properties of the patches. The physical appearances including the translucent, color thickness and weight of the patches were recorded. The mechanical properties and skin adhesion of the patches were determined by a texture analyzer. The polymorphism of CM in the patches and the release profile of CM from the patches were investigated by X-ray diffraction and Franz diffusion cell, respectively. CM transdermal patches were translucent. The weight and thickness of the patches increased as the amount of additive increased. Glycerin and PG decreased the strength of the patches, while PEG increased the hardness. Adding CM to the patches increased the hardness and decreased the elasticity of the patches. The internal structure of CM loaded into the patches was an amorphous form. The CM patches exhibited some adhesion properties when contacted with the porcine skin. The release of CM from the patches was found to be 71-108% within 60 minutes. The patch prepared from 10% HPMC, 15% Glycerin, and 5% PG displayed the highest release rate. In conclusion, the CM loaded HPMC patches presented desirable properties, which could be used as a transdermal patch for the treatment of acne.

Abstract: Spray-dried emulsion is one of the useful strategies to enhance dissolution properties of poorly water-soluble drug for example resveratrol. Physical properties i.e. particle size and moisture content of spray-dried emulsions could affect their quality attributes. In this study, Box-Behnken design was performed in order to determine effect of formulation and spray drying condition parameters i.e. feed rate on responses including particle size and moisture content of resveratrol spray-dried emulsions. The spray-dried emulsions were prepared by varying content of low-methoxyl pectin (LMP) and caprylic/capric glycerides (CCG) and sprayed at different feed rate. Box-Behnken design results reveled that the particle size of spray-dried emulsions was significantly influenced by the content of LMP, interactions between LMP and CCG, interactions between LMP and feed rate. LMP content showed positive relationships with the particle size. The content of CCG had negative significantly effect on moisture content of the spray-dried emulsion. Mathematical models describing the relationships between studied parameters and responses provided good predictability. Based on model, the optimal formulation was prepared using 2.6% w/w of LMP, 9% w/w of CCG, and feed rate of 6.8 mL/min and the small particle size (~5.9 μm) and low moisture content (~5.6%) were obtained. The spray-dried emulsions were successfully prepared with satisfy quality. The Box-Behnken design would be an effective tool to elucidate influence of formulation and spray drying conditions on particle size and moisture content of the spray-dried emulsions. Further, the design aided in developing and optimizing the spray-dried emulsions with specified quality.