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Pilot Formulation Study of Ph-sensitive Gels

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24 ago 2023

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Figure 1.

Appearance of formulation C940-0.1 (a) solution, (b) gel, PCP-0.225 (c) solution, (d) gel, CHM-2.5 (e) solution.
Appearance of formulation C940-0.1 (a) solution, (b) gel, PCP-0.225 (c) solution, (d) gel, CHM-2.5 (e) solution.

Figure 2.

Dissolution profiles and Korsmeyer-Peppas fitting lines of formulations C940-0.1 (○, – • –), PCP-0.225 (▲, ‒‒‒) and CHM-2.5 (□, - - -).
Dissolution profiles and Korsmeyer-Peppas fitting lines of formulations C940-0.1 (○, – • –), PCP-0.225 (▲, ‒‒‒) and CHM-2.5 (□, - - -).

Composition of polymeric solutions (in grams)_

Formulation C940 PCP CHL CHM PW AA 1%
C940-0.10 0.100 - - - 99.900 -
C940-0.70 0.700 - - - 99.300 -
C940-1.30 1.300 - - - 98.700 -
PCP-0.200 - 0.200 - - 99.800 -
PCP-0.225 - 0.225 - - 99.775 -
PCP-0.250 - 0.250 - - 99.750 -
PCP-0.300 - 0.300 - - 99.700 -
PCP-0.400 - 0.400 - - 99.600 -
PCP-0.600 - 0.600 - - 99.400 -
PCP-1.000 - 1.000 - - 99.000 -
CHL-3000 - - 3.000 - - 97.000
CHL-3.50. - - 3.500 - - 96.500
CHM-200. - - - 2.000 - 98.000
CHM-2.50 - - - 2.500 - 97.500
CHM-30.0 - - - 3.000 - 97.000

Injectability of polymeric solutions_

Formulation Injection needle diameter
0.5 0.6 0.7 0.8
C940-0.10 + + + +
C940-0.70
C940-1.30
PCP-0.200 + + + +
PCP-0.225 + + + +
PCP-0.250 + + + +
PCP-0.300 + + + +
PCP-0.400 + + + +
PCP-0.600 + + + +
PCP-1.000 + + + +
CHL-3000
CHL-3.50.
CHM-200.
CHM-2.50
CHM-30.0

Appearance of polymeric solutions and gels, pH of polymeric solutions, and pH of the gelation_

Formulation Appearance pH
polymeric solution gel polymeric solution gelation
C940-0.10 ++ +++ 3.57 ± 0.05 6.74 ± 0.47
C940-0.70 ++ +++ 2.93 ± 0.10 3.01 ± 0.14
C940-1.30 ++ +++ 2.66 ± 0.03 2.81 ± 0.02
PCP-0.200 + 3.68 ± 0.02
PCP-0.225 + +++ 3.59 ± 0.05 6.61 ± 0.21
PCP-0.250 + +++ 3.56 ± 0.03 6.02 ± 0.06
PCP-0.300 + +++ 3.39 ± 0.03 5.36 ± 0.30
PCP-0.400 + +++ 3.35 ± 0.04 4.19 ± 0.33
PCP-0.600 + ++ 3.26 ± 0.04 4.03 ± 0.08
PCP-1.000 + + 3.32 ± 0.24 3.36 ± 0.37
CHL-3000 + np 4.62 ± 0.09 7.00 ± 0.00
CHL-3.50. + np 5.05 ± 0.02 6.50 ± 0.00
CHM-200. ++ np 4.33 ± 0.02 9.00 ± 0.00
CHM-2.50 + np 4.52 ± 0.01 6.00 ± 0.00
CHM-30.0 + np 4.85 ± 0.01 6.00 ± 0.00

Dissolution parameters of the Korsmeyer–Peppas model and released amount of the drug after 60 min dissolution_

Formulation kKP n Tlag T50 Q60
C940-0.10 22.98 ± 4.95 0.31 ± 0.03 2.72 ± 0.21 16.54 ± 05.37 77.04 ± 5.94
PCP-0.225 19.70 ± 2.86 0.24 ± 0.04 4.04 ± 0.27 61.01 ± 20.48 48.85 ± 5.74
CHM-2.50 16.52 ± 3.42 0.39 ± 0.04 1.45 ± 0.61 19.29 ± 04.88 77.35 ± 4.98

Calculated adjusted coefficient of determination (R2adj) of different mathematical models, fitted to released data in whole dissolution time (0–60 min)_

Formulation R2adj of mathematical models
Zero order First order Korsmeyer–Peppas
C940-0.10 0.741 ± 0.046 0.975 ± 0.003 0.999 ± 0.001
PCP-0.225 0.637 ± 0.077 0.993 ± 0.002 0.990 ± 0.003
CHM-2.50 0.792 ± 0.032 0.956 ± 0.008 0.969 ± 0.004

Process parameters of preparation for individual polymers_

Polymer Primary stirring (rpm) Secondary stirring (rpm) Homogenization time (min)
Carbomer 300 330 30
Polycarbophil 300 350 45
Chitosan 500 700 45
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