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Nicotinamide polymeric nanoemulsified systems: a quality-by-design case study for a sustained antimicrobial activity.

Zidan AS, Ahmed OA, Aljaeid BM - Int J Nanomedicine (2016)

Bottom Line: EC, EE, particle size, polydispersity index, zeta potential, and percentage release in 24 hours were found to be in the range of 33.5%-68.8%, 53.1%-67.1%, 43.3-243.3 nm, 0.08-0.28, 9.5-53.3 mV, and 5.8%-22.4%, respectively.One-way analysis of variance and Pareto charts revealed that the experimental loadings of 2-hydroxypropyl-β-cyclodextrin and Eudragit(®) S100 were the most significant for their effects on nicotinamide EC and EE.In conclusion, the study demonstrated the potential of polymeric nanoemulsified system to sustain the release and antibacterial activity of nicotinamide.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

ABSTRACT
Nicotinamide, the amide form of vitamin B3, was demonstrated to combat some of the antibiotic-resistant infections that are increasingly common around the world. The objective of this study was to thoroughly understand the formulation and process variabilities affecting the preparation of nicotinamide-loaded polymeric nanoemulsified particles. The quality target product profile and critical quality attributes of the proposed product were presented. Plackett-Burman screening design was employed to screen eight variables for their influences on the formulation's critical characteristics. The formulations were prepared by an oil-in-water emulsification followed by solvent replacement. The prepared systems were characterized by entrapment capacity (EC), entrapment efficiency (EE), particle size, polydispersity index, zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, in vitro drug release, and their antibacterial activity against bacterial scrums. EC, EE, particle size, polydispersity index, zeta potential, and percentage release in 24 hours were found to be in the range of 33.5%-68.8%, 53.1%-67.1%, 43.3-243.3 nm, 0.08-0.28, 9.5-53.3 mV, and 5.8%-22.4%, respectively. One-way analysis of variance and Pareto charts revealed that the experimental loadings of 2-hydroxypropyl-β-cyclodextrin and Eudragit(®) S100 were the most significant for their effects on nicotinamide EC and EE. Moreover, the polymeric nanoemulsified particles demonstrated a sustained release profile for nicotinamide. The Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction demonstrated a significant interaction between the drug and 2-hydroxypropyl-β-cyclodextrin that might modulate the sustained release behavior. Furthermore, the formulations provided a sustained antibacterial activity that depended on nicotinamide-loading concentration, release rate, and incubation time. In conclusion, the study demonstrated the potential of polymeric nanoemulsified system to sustain the release and antibacterial activity of nicotinamide.

No MeSH data available.


Related in: MedlinePlus

Pareto charts of the main effects of variables on the investigated responses.Notes: X1–X8 are Eudragit S100, HP-β-CD and drug loadings (mg), volumes of organic and aqueous phases (mL), ultrasonication time (s) and amplitude (%), and level of MgCl2 as a stabilizer (%), respectively.Abbreviations: HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; PDI, polydispersity index.
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f3-ijn-11-1501: Pareto charts of the main effects of variables on the investigated responses.Notes: X1–X8 are Eudragit S100, HP-β-CD and drug loadings (mg), volumes of organic and aqueous phases (mL), ultrasonication time (s) and amplitude (%), and level of MgCl2 as a stabilizer (%), respectively.Abbreviations: HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; PDI, polydispersity index.

Mentions: Out of three formulation variables, two factors were significant for their effects on EC and EE, namely HP-β-CD and Eudragit loading concentrations. On the other hand, ultrasonic parameters and volume of aqueous and organic phases were the significant processing parameters in both responses. As shown in Table 4 and Figure 3, HP-β-CD level showed the highest significant effect on the resultant EC (P=0.0057) followed by ultrasonic time (P=0.0294). On the other hand, volume of the organic phase was the most important factor that controlled nicotinamide EE followed by Eudragit concentration and ultrasonic amplitude. Positive relationships were observed by increasing both HP-β-CD and Eudragit loading concentrations (Figure 4), with maximum EC and EE of 68% and 67%, respectively, occurring at approximately 200 mg HP-β-CD and 200 mg Eudragit S100 experimental loadings. On the other hand, a negative curvature was observed (Figure 4) by increasing ultrasonic time and amplitude with minimum EC and EE of 33% and 53%, respectively, obtained under ultrasonic time and amplitude of 180 seconds and 60%, respectively. The marked positive effect of HP-β-CD on EC can be described by the structural configuration of the branched copolymer, HP-β-CD, which encompasses a cyclic oligosaccharide with seven D-glucose moieties linked by an α-1,4-glucosidic bond. This structure would provide a rigid configuration in which the primary –OH groups are oriented toward the narrow side and the secondary –OH groups are on the wide side of the torus. Having this configuration, HP-β-CD would form a hydrophilic outer surface and hydrophobic inner cavity to entrap whole or part of drug molecules, hence providing a molecular shield with minimal leakage through inner cavity.25,26 The negative effect of the organic phase volume of EE would be ascribed by decreasing the viscosity of the internal phase. This would facilitate the shearing action to leach out drug molecules out of the formed matrix. The negative effects of the ultrasonication parameters on both EC and EE might be explained by the drug leakage and precipitation as the formulation was subjected to long ultrasonication time (180 seconds) and power (60% amplitude). The significant positive influence of Eudragit S100 on the resultant EE would be ascribed to its hydrophobic methacrylate structure. Eudragit S100 encompasses an anionic copolymerization product of methacrylic acid and methyl methacrylate to impart a thick polymeric surface to the formed nanomicelles. Moreover, the low density of quaternary ammonium groups in Eudragit S100 would limit nicotinamide diffusion to the aqueous medium.27


Nicotinamide polymeric nanoemulsified systems: a quality-by-design case study for a sustained antimicrobial activity.

Zidan AS, Ahmed OA, Aljaeid BM - Int J Nanomedicine (2016)

Pareto charts of the main effects of variables on the investigated responses.Notes: X1–X8 are Eudragit S100, HP-β-CD and drug loadings (mg), volumes of organic and aqueous phases (mL), ultrasonication time (s) and amplitude (%), and level of MgCl2 as a stabilizer (%), respectively.Abbreviations: HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; PDI, polydispersity index.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835127&req=5

f3-ijn-11-1501: Pareto charts of the main effects of variables on the investigated responses.Notes: X1–X8 are Eudragit S100, HP-β-CD and drug loadings (mg), volumes of organic and aqueous phases (mL), ultrasonication time (s) and amplitude (%), and level of MgCl2 as a stabilizer (%), respectively.Abbreviations: HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; PDI, polydispersity index.
Mentions: Out of three formulation variables, two factors were significant for their effects on EC and EE, namely HP-β-CD and Eudragit loading concentrations. On the other hand, ultrasonic parameters and volume of aqueous and organic phases were the significant processing parameters in both responses. As shown in Table 4 and Figure 3, HP-β-CD level showed the highest significant effect on the resultant EC (P=0.0057) followed by ultrasonic time (P=0.0294). On the other hand, volume of the organic phase was the most important factor that controlled nicotinamide EE followed by Eudragit concentration and ultrasonic amplitude. Positive relationships were observed by increasing both HP-β-CD and Eudragit loading concentrations (Figure 4), with maximum EC and EE of 68% and 67%, respectively, occurring at approximately 200 mg HP-β-CD and 200 mg Eudragit S100 experimental loadings. On the other hand, a negative curvature was observed (Figure 4) by increasing ultrasonic time and amplitude with minimum EC and EE of 33% and 53%, respectively, obtained under ultrasonic time and amplitude of 180 seconds and 60%, respectively. The marked positive effect of HP-β-CD on EC can be described by the structural configuration of the branched copolymer, HP-β-CD, which encompasses a cyclic oligosaccharide with seven D-glucose moieties linked by an α-1,4-glucosidic bond. This structure would provide a rigid configuration in which the primary –OH groups are oriented toward the narrow side and the secondary –OH groups are on the wide side of the torus. Having this configuration, HP-β-CD would form a hydrophilic outer surface and hydrophobic inner cavity to entrap whole or part of drug molecules, hence providing a molecular shield with minimal leakage through inner cavity.25,26 The negative effect of the organic phase volume of EE would be ascribed by decreasing the viscosity of the internal phase. This would facilitate the shearing action to leach out drug molecules out of the formed matrix. The negative effects of the ultrasonication parameters on both EC and EE might be explained by the drug leakage and precipitation as the formulation was subjected to long ultrasonication time (180 seconds) and power (60% amplitude). The significant positive influence of Eudragit S100 on the resultant EE would be ascribed to its hydrophobic methacrylate structure. Eudragit S100 encompasses an anionic copolymerization product of methacrylic acid and methyl methacrylate to impart a thick polymeric surface to the formed nanomicelles. Moreover, the low density of quaternary ammonium groups in Eudragit S100 would limit nicotinamide diffusion to the aqueous medium.27

Bottom Line: EC, EE, particle size, polydispersity index, zeta potential, and percentage release in 24 hours were found to be in the range of 33.5%-68.8%, 53.1%-67.1%, 43.3-243.3 nm, 0.08-0.28, 9.5-53.3 mV, and 5.8%-22.4%, respectively.One-way analysis of variance and Pareto charts revealed that the experimental loadings of 2-hydroxypropyl-β-cyclodextrin and Eudragit(®) S100 were the most significant for their effects on nicotinamide EC and EE.In conclusion, the study demonstrated the potential of polymeric nanoemulsified system to sustain the release and antibacterial activity of nicotinamide.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

ABSTRACT
Nicotinamide, the amide form of vitamin B3, was demonstrated to combat some of the antibiotic-resistant infections that are increasingly common around the world. The objective of this study was to thoroughly understand the formulation and process variabilities affecting the preparation of nicotinamide-loaded polymeric nanoemulsified particles. The quality target product profile and critical quality attributes of the proposed product were presented. Plackett-Burman screening design was employed to screen eight variables for their influences on the formulation's critical characteristics. The formulations were prepared by an oil-in-water emulsification followed by solvent replacement. The prepared systems were characterized by entrapment capacity (EC), entrapment efficiency (EE), particle size, polydispersity index, zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, in vitro drug release, and their antibacterial activity against bacterial scrums. EC, EE, particle size, polydispersity index, zeta potential, and percentage release in 24 hours were found to be in the range of 33.5%-68.8%, 53.1%-67.1%, 43.3-243.3 nm, 0.08-0.28, 9.5-53.3 mV, and 5.8%-22.4%, respectively. One-way analysis of variance and Pareto charts revealed that the experimental loadings of 2-hydroxypropyl-β-cyclodextrin and Eudragit(®) S100 were the most significant for their effects on nicotinamide EC and EE. Moreover, the polymeric nanoemulsified particles demonstrated a sustained release profile for nicotinamide. The Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction demonstrated a significant interaction between the drug and 2-hydroxypropyl-β-cyclodextrin that might modulate the sustained release behavior. Furthermore, the formulations provided a sustained antibacterial activity that depended on nicotinamide-loading concentration, release rate, and incubation time. In conclusion, the study demonstrated the potential of polymeric nanoemulsified system to sustain the release and antibacterial activity of nicotinamide.

No MeSH data available.


Related in: MedlinePlus