Modified Potato Starch as a Potential Retardant for Prolonged Release of Lidocaine Hydrochloride from Methylcellulose Hydrophilic Gel

Abstract

The problem of drug delivery often concentrates on the prolongation of drug activity. Application of natural polymers which are biodegradable and inexpensive is in the interest of many researchers. The aim of this study was the application of newly synthesized starch derivatives as potential functional excipients proposed for hydrophilic gel with lidocaine hydrochloride (LH) to prolong drug release from the hydrogel matrix. In our study, we investigated the effect of starch modified with citric acid on the release kinetics of LH using UV-VIS and Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), as well as viscosity and pH measurements. We demonstrated the effectiveness of citric-acid-modified starch in prolonging the release of LH from methylcellulose gel.

Keywords: lidocaine hydrochloride; modified starch; release study.

Figure 1

Structural patterns of lidocaine hydrochloride monohydrate (a) and of starch modified by citric acid cross-linking (b).

Figure 2

(A) The release course of LH from the formulation doped with low level of S1 (F0: -◊-, green markers). (B) The release course of LH from formulations doped with S1 and S2 (F1: -○-, red markers; F2: -▫-, yellow markers). (C) The release course of LH from formulations doped with S3 and S4 (F3: -●-, red markers; F4 -▪-, yellow markers). The plots on (A–C) are compared to methylcellulose gel (REF: -∆-, blue markers). (D) The percent of released LH after 2 h (shaded columns) and after 24 h (non-shaded columns). The abbreviations S1–S4, as well as F0–F4, REF are elucidated in Table 1 and Table 2, respectively. According to the Student’s t-test with Bonferroni correction, there is no statistical significance of the tested formulations in relation to the reference sample (α = 0.01).

Figure 2

(A) The release course of LH from the formulation doped with low level of S1 (F0: -◊-, green markers). (B) The release course of LH from formulations doped with S1 and S2 (F1: -○-, red markers; F2: -▫-, yellow markers). (C) The release course of LH from formulations doped with S3 and S4 (F3: -●-, red markers; F4 -▪-, yellow markers). The plots on (A–C) are compared to methylcellulose gel (REF: -∆-, blue markers). (D) The percent of released LH after 2 h (shaded columns) and after 24 h (non-shaded columns). The abbreviations S1–S4, as well as F0–F4, REF are elucidated in Table 1 and Table 2, respectively. According to the Student’s t-test with Bonferroni correction, there is no statistical significance of the tested formulations in relation to the reference sample (α = 0.01).

Figure 3

FTIR spectra of LH, modified starch (S1–S4) and experimental formulations of lidocaine hydrochloride with modified starch (HS1–HS4); (a–d) respectively. The abbreviations HS1–HS4 are elucidated in Table 4.

Figure 3

FTIR spectra of LH, modified starch (S1–S4) and experimental formulations of lidocaine hydrochloride with modified starch (HS1–HS4); (a–d) respectively. The abbreviations HS1–HS4 are elucidated in Table 4.

Figure 4

The DSC thermograms of lidocaine hydrochloride (LH); (a,c,e,g) thermograms of the first heating cycle; (b,d,f,h) thermograms of the second heating cycle, modified starch (S1–S4) and experimental formulations of LH with modified starch (HS1–HS4). The abbreviations HS1–HS4 are elucidated in Table 4.

Figure 4

The DSC thermograms of lidocaine hydrochloride (LH); (a,c,e,g) thermograms of the first heating cycle; (b,d,f,h) thermograms of the second heating cycle, modified starch (S1–S4) and experimental formulations of LH with modified starch (HS1–HS4). The abbreviations HS1–HS4 are elucidated in Table 4.

Figure 5

The viscosity of evaluated formulations F1–F4 and reference formulation REF (methylcellulose hydrogel). The red line refers to the mean viscosity of the REF. The abbreviations F0–F4 and REF are elucidated in the Table 2. An asterisk denotes the non-statistical significance of the formulation data according to the ANOVA statistical test for α = 0.05.

Figure 6

The pH of modified starch, S1: -○-; S2: -▫-; S3: -●-; S4: -▪- (A), applied in the respective evaluated formulations F1–F4 and reference formulation REF, and the pH of formulations F1–F4 and REF (B). The abbreviations S1–S4, as well as F1–F4 and REF are elucidated in the Table 1 and Table 2, respectively. The statistical significance of the formulation data observed according to the ANOVA statistical test for α = 0.05 (p < 0.05).

Figure 7

The SEM microphotographs of modified starch S1 (A), S3 (B), S2 (C) and S4 (D). The abbreviations S1–S4 are elucidated in the Table 1. The bar on the left on every microphotograph represents 20 µm, whereas on the enlargement (inserts right-above) the bar represents 10 µm.