Comparison of Rheological, Drug Release, and Mucoadhesive Characteristics upon Storage between Hydrogels with Unmodified or Beta-Glycerophosphate-Crosslinked Chitosan

Table 3

Changes in organoleptic properties, clotrimazole content, and drug particle size in hydrogels with unmodified CS (F1, F2) or with bGP-crosslinked CS (F3, F4) upon storage compared to values obtained to freshly prepared formulations.

Storage time (months)	Parameter	Hydrogel with
		Unmodified CS			bGP-crosslinked CS
		F1	F2	F3	F4
0	pH	4.06 ± 0.02	4.08 ± 0.01	4.54 ± 0.04	4.56 ± 0.03
	Particle size range (μm)	6.0–49.5	6.0–47.0	4.0–40.0	4.0–41.5
	Drug content (%)	95.6 ± 4.9	98.2 ± 3.5	97.3 ± 4.1	97.4 ± 3.3
25°C/60% RH
1	pH	4.16 ± 0.05	4.23 ± 0.05	4.51 ± 0.04	4.53 ± 0.02
	Particle size range (μm)	7.5–52.5	7.5–57.0	6.0–29.5	5.0–48.5
	Drug content (%)	94.8 ± 3.3	96.1 ± 4.2	96.5 ± 3.5	97.1 ± 3.9
3	pH	4.40 ± 0.02	4.38 ± 0.03	4.35 ± 0.02	4.27 ± 0.03
	Particle size range (μm)	7.0–58.0	6.0–54.5	4.0–41.0	4.0–34.5
	Drug content (%)	94.6 ± 5.9	92.4 ± 5.1	98.1 ± 4.1	95.2 ± 4.5
6	pH	4.31 ± 0.02	4.39 ± 0.01	4.26 ± 0.02	4.23 ± 0.02
	Particle size range (μm)	n.d.	n.d.	Sedimentation	Sedimentation
	Drug content (%)	n.d.	n.d.	n.d.	n.d.
40°C/75% RH
1	pH	4.20 ± 0.03	4.24 ± 0.05	4.56 ± 0.04	4.51 ± 0.02
	Particle size diameter (μm)	Sedimentation	Sedimentation	10.0–53.0	5.0–61.0
	Drug content (%)	n.d.	n.d.	96.5 ± 3.5	97.1 ± 3.9
3	pH	4.40 ± 0.02	4.48 ± 0.02	4.36 ± 0.01	4.29 ± 0.03
	Particle size range (μm)	n.d.	n.d.	5.0–44.5	4.5–37.0
	Drug content (%)	n.d.	n.d.	93.1 ± 7.1	94.2 ± 6.8
4 ± 2°C
1	pH	4.10 ± 0.05	4.03 ± 0.05	4.56 ± 0.04	4.53 ± 0.02
	Particle size range (μm)	12.0–58.5	7.5–65.0	8.0–59.0	10.5–45.0
	Drug content (%)	94.3 ± 3.8	96.1 ± 4.2	96.5 ± 3.5	97.1 ± 3.9
3	pH	4.10 ± 0.02	4.12 ± 0.02	4.31 ± 0.02	4.37 ± 0.03
	Particle size range (μm)	Sedimentation	6.0–59.5	11.0–40.0	5.0–45.5
	Drug content (%)	n.d.	95.1 ± 8.4	98.1 ± 4.7	95.2 ± 4.5
6	pH	4.23 ± 0.03	4.29 ± 0.03	4.28 ± 0.03	4.37 ± 0.01
	Particle size range (μm)	n.d.	n.d.	6.5–46.0	5.0–40.0
	Drug content (%)	n.d.	n.d.	94.1 ± 4.9	96.0 ± 3.7

, mean ± SD; n.d.: not determined.