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Optimization of Metronidazole Emulgel.

Rao M, Sukre G, Aghav S, Kumar M - J Pharm (Cairo) (2013)

Bottom Line: The statistical validity of the polynomials was established, and optimized formulation factors were selected.Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology.Emulgel system of MTZ was developed and optimized using 2(3) factorial design and could provide an effective treatment against topical infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Maharashtra, Pune 411 001, India.

ABSTRACT
The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h (Y 1) and spreadability (Y 2). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y 1 and Y 2. The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 2(3) factorial design and could provide an effective treatment against topical infections.

No MeSH data available.


Related in: MedlinePlus

Response surface plot showing effect of (a) oil (X1) and (b) Gelling agent (X3) on responses percent drug release (Y1) and spreadability (Y2).
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fig4: Response surface plot showing effect of (a) oil (X1) and (b) Gelling agent (X3) on responses percent drug release (Y1) and spreadability (Y2).

Mentions: A three-factor, two-level full factorial experimental design was used to optimize the formulation variables as the response surface methodology requires 8 experiments. The independent variables and the responses for all 8 experimental runs are given in Table 2. The 3D response surface plots drawn using Design Expert software are shown in Figure 4. Based on the results of pseudoternary phase diagrams, appropriate ranges of the components were chosen. The oil phase concentration that could form microemulsion was found to be 10–70% and was selected as oil concentration to identify the optimum proportion of oil. Previous reports revealed that there was a really tight relationship between the hydration effect of the stratum corneum and the dermal permeation [9], and the thermodynamic activity of drug in microemulsions was a significant driving force for the release and penetration of drug into skin [9]. Based on pseudoternary phase diagrams, the surfactant mixture (surfactant, cosurfactant, and Smix 2 : 1), that could form clear microemulsion with large area was selected as variable and was found to be 25–55%. Design Expert software was used to optimize the formulation and to develop the mathematical equations which are depicted in (5) and (6). The responses, percent drug diffusion (Y1) and spreadability (Y2) were found to be significantly higher (Y1, 93.16–83.06%; Y2, 25.87–19.54 gm·cm/sec) only when the oil and Smix were used at 10% (v/v) and 55%  (v/v) concentration level, respectively. The ranges of other responses, Y1 and Y2 were 68.06–93.16% and 7.76–25.87 gm·cm/sec, respectively. The responses of these formulations ranged from a low drug diffusion of 68.60% (F8, high level of oil and Smix and of high level of gelling agent) to a higher penetration of 93.16% (F3, low level of oil, high level of Smix, and low level of gelling agent). For estimation of quantitative effects of the different combination of factors and factor levels on percent drug diffusion and spreadability, the response surface models were calculated with Design Expert software by applying coded values of factor levels. The model described could be represented as(5)Y1(percent  drug  diffusion) =81.36−2.80X1+1.5X2−0.25X3  −1.43X1X2−1.52X1X2X3,(6)Y2(spreadability) =13.33−3.45X1+1.57X2−3.44X3  −2.49X1X2−1.23X1X2X3.


Optimization of Metronidazole Emulgel.

Rao M, Sukre G, Aghav S, Kumar M - J Pharm (Cairo) (2013)

Response surface plot showing effect of (a) oil (X1) and (b) Gelling agent (X3) on responses percent drug release (Y1) and spreadability (Y2).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590800&req=5

fig4: Response surface plot showing effect of (a) oil (X1) and (b) Gelling agent (X3) on responses percent drug release (Y1) and spreadability (Y2).
Mentions: A three-factor, two-level full factorial experimental design was used to optimize the formulation variables as the response surface methodology requires 8 experiments. The independent variables and the responses for all 8 experimental runs are given in Table 2. The 3D response surface plots drawn using Design Expert software are shown in Figure 4. Based on the results of pseudoternary phase diagrams, appropriate ranges of the components were chosen. The oil phase concentration that could form microemulsion was found to be 10–70% and was selected as oil concentration to identify the optimum proportion of oil. Previous reports revealed that there was a really tight relationship between the hydration effect of the stratum corneum and the dermal permeation [9], and the thermodynamic activity of drug in microemulsions was a significant driving force for the release and penetration of drug into skin [9]. Based on pseudoternary phase diagrams, the surfactant mixture (surfactant, cosurfactant, and Smix 2 : 1), that could form clear microemulsion with large area was selected as variable and was found to be 25–55%. Design Expert software was used to optimize the formulation and to develop the mathematical equations which are depicted in (5) and (6). The responses, percent drug diffusion (Y1) and spreadability (Y2) were found to be significantly higher (Y1, 93.16–83.06%; Y2, 25.87–19.54 gm·cm/sec) only when the oil and Smix were used at 10% (v/v) and 55%  (v/v) concentration level, respectively. The ranges of other responses, Y1 and Y2 were 68.06–93.16% and 7.76–25.87 gm·cm/sec, respectively. The responses of these formulations ranged from a low drug diffusion of 68.60% (F8, high level of oil and Smix and of high level of gelling agent) to a higher penetration of 93.16% (F3, low level of oil, high level of Smix, and low level of gelling agent). For estimation of quantitative effects of the different combination of factors and factor levels on percent drug diffusion and spreadability, the response surface models were calculated with Design Expert software by applying coded values of factor levels. The model described could be represented as(5)Y1(percent  drug  diffusion) =81.36−2.80X1+1.5X2−0.25X3  −1.43X1X2−1.52X1X2X3,(6)Y2(spreadability) =13.33−3.45X1+1.57X2−3.44X3  −2.49X1X2−1.23X1X2X3.

Bottom Line: The statistical validity of the polynomials was established, and optimized formulation factors were selected.Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology.Emulgel system of MTZ was developed and optimized using 2(3) factorial design and could provide an effective treatment against topical infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Maharashtra, Pune 411 001, India.

ABSTRACT
The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h (Y 1) and spreadability (Y 2). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y 1 and Y 2. The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 2(3) factorial design and could provide an effective treatment against topical infections.

No MeSH data available.


Related in: MedlinePlus