# Freeze-Drying Ethlycellulose Microparticles Loaded with
## 3 Results and Discussion
### In Vitro Release Study of the Ethylcellulose Microparticles Loaded with ETO
The established controlled release formulations were found to be successful in offering the prolonged release of FLT over a long period of time after an appropriate initial burst release [39]. The same results were also reported by [PERSON] et al., who formulated budesonide (BDS)/cyclodextrinrin (CD) complex-loaded and lyophilized microparticles. The dissolution of BDS was enhanced compared to pure BDS and the hydrophilic polymers. Thus, prepared lyophilized microparticles, including drug-CD complexes, can be potential carriers for the more soluble polymer delivery of BDS [40]. To describe the dissolution kinetics of the prepared microparticles (before freeze-drying) at pH 7.4, five equations were used, namely, the first order, zero order, Hixson-Crowell, Higuchi, and Peppas equations. Table 1 shows the best equations that fit the dissolution data for all ET-ETO microparticle formulations used in this study. The results showed that ET-ETO microparticles with drug-polymer ratios of 1:1, 1:6, and 1:20 fit best \begin{table}
\begin{tabular}{c c c c c c} \hline
**Ratio of** & **Zero-Order** & **First-Order** & **Higuchi** & **Hixson–Crowell** & \\
**Etposide/** & **Dissolution Rate** & **Dissolution Rate** & **Dissolution Rate** & **Dissolution Rate** & **Peppas Constant** \\
**Ethycellulose** & **Constant** & **Constant** & **Constant** & **Constant** & **Constant** \\ \hline \hline \multirow{3}{*}{Free drug} & K = 4.76 & K = 0.28 & K = 0.22 & K = 19.8 & \\  & r\({}^{2}\) = 0.55 & r\({}^{2}\) = 0.85 & r\({}^{2}\) = 0.87 & r\({}^{2}\) = 0.73 & 0.25 \\  & K = 7.23 & K = 0.14 & K = 0.17 & K = 28.9 & \\  & r\({}^{2}\) = 0.72 & r\({}^{2}\) = 0.82 & r\({}^{2}\) = 0.95 & r\({}^{2}\) = 0.89 & 0.57 \\  & K = 6.43 & K = 0.09 & K = 0.12 & K = 25.5 & \\  & r\({}^{2}\) = 0.75 & r\({}^{2}\) = 0.69 & r\({}^{2}\) = 0.87 & r\({}^{2}\) = 0.91 & 0.65 \\  & K = 8.30 & K = 0.15 & K = 0.19 & K = 32.4 & \\  & r\({}^{2}\) = 0.79 & r\({}^{2}\) = 0.88 & r\({}^{2}\) = 0.97 & r\({}^{2}\) = 0.93 & 0.72 \\  & K = 7.91 & K = 0.12 & K = 0.16 & K = 30.2 & \\  & r\({}^{2}\) = 0.84 & r\({}^{2}\) = 0.90 & r\({}^{2}\) = 0.95 & r\({}^{2}\) = 0.94 & 0.80 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Peppas constants and dissolution rate constants according to the zero-order, first-order, Higuchi, and Hixson–Crowell equations. Figure 7: Dissolution profiles at pH 7.4 for free etoposide and freeze-dried ET-ETO microparticles prepared at different drug–polymer ratios. to the Higuchi equation with r\({}^{2}\) values equal to 0.95, 0.97, and 0.95, respectively. The dissolution data for the ET-ETO microparticles with a drug-polymer ratio of 1:3 fit best to the Hixson-Crowell equation, with an r\({}^{2}\) value equal to 0.91. The application of the linear form of the Peppas equation to the dissolution data showed that the dissolution mechanism was Fickian diffusion for free ETO with a Peppas constant (n) less than 0.45 (n = 0.254), as shown in Table 1. Additionally, the results from Table 1 show that the release from all prepared microparticles in this study was non-Fickian transport (anomalous) with Peppas constants (n) equal to 0.57, 0.65, 0.72, and 0.80 for microparticles with drug-polymer ratios of 1:1, 1:3, 1:6, and 1:20, respectively. [PERSON] et al. showed the same results for the release kinetics of all formulas for cetuximab-conjugated octreotide loaded with alginate beads. This mechanism was best suited to the Hixson-Crowell equation [14].