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. 2020 Jun 22;14:2435-2448.
doi: 10.2147/DDDT.S244016. eCollection 2020.

Artificial Neural Network (ANN) Approach to Predict an Optimized pH-Dependent Mesalamine Matrix Tablet

Asad Majeed Khan  1   2 , Muhammad Hanif  1 , Nadeem Irfan Bukhari  3 , Rahat Shamim  3 , Fatima Rasool  3 , Sumaira Rasul  4 , Sana Shafique  5
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Artificial Neural Network (ANN) Approach to Predict an Optimized pH-Dependent Mesalamine Matrix Tablet

Asad Majeed Khan et al. Drug Des Devel Ther. .
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Abstract

Background: Severe bleeding and perforation of the colon and rectum are complications of ulcerative colitis which can be treated by a targeted drug delivery system.

Purpose: Development of colon-targeted delivery usually involves a complex formulation process and coating steps of pH-sensitive methacrylic acid based Eudragit®. The current work was purposefully designed to develop dicalcium phosphate (DCP) facilitated with Eudragit-S100-based pH-dependent, uncoated mesalamine matrix tablets.

Materials and methods: Mesalamine formulations were compressed using wet granulation technique with varying compositions of dicalcium phosphate (DCP) and Eudragit-S100. The developed formulations were characterized for physicochemical and drug release profiles. Infrared studies were carried out to ensure that there was no interaction between active ingredients and excipients. Artificial neural network (ANN) was used for the optimization of final DCP-Eudragit-S100 complex and the experimental data were employed to train a multi-layer perception (MLP) using quick propagation (QP) training algorithm until a satisfactory root mean square error (RMSE) was reached. The ANN-aided optimized formulation was compared with commercially available Masacol®.

Results: Compressed tablets met the desirability criteria in terms of thickness, hardness, weight variation, friability, and content uniformity, ie, 5.34 mm, 7.7 kg/cm2, 585±5 mg (%), 0.44%, and 103%, respectively. In-vitro dissolution study of commercially available mesalamine and optimized formulation was carried out and the former showed 100% release at 6 h while the latter released only 12.09% after 2 h and 72.96% after 12 h which was fitted to Weibull release model with b value of 1.3, indicating a complex release mechanism.

Conclusion: DCP-Eudragit-S100 blend was found explicative for mesalamine release without coating in gastric and colonic regions. This combination may provide a better control of ulcerative colitis.

Keywords: DCP-Eudragit-S100 complex; Weibull release model; phosphatidylserine; ulcerative colitis.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

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Figure 1
Figure 1
Scheme of study showing five stages of compression: Mix, GS-1, GS-2, F-mix and compression and structure of ANN applied using quick propagation method for data learning algorithm.
Figure 2
Figure 2
Percentage release studies of mesalamine from formulation F1-F11 using 0.2 M HCl for 2 h at pH 1.2 and 0.2 M phosphate buffer at pH 7.2 for further 6 h.
Figure 3
Figure 3
Percentage release studies of mesalamine from formulation F12-F22 using 0.2 M HCl for 2 h at pH 1.2 and 0.2 M phosphate buffer at pH 7.2 for further 6 h.
Figure 4
Figure 4
Comparative % release studies of mesalamine from formulation F23-F24 with reference release data using 0.2 M HCl for 2 h at pH 1.2 and 0.2 M phosphate buffer at pH 7.2 for further 10 h.
Figure 5
Figure 5
Relative significance of ingredients for the mesalamine colonic system for overall properties of formulation which were ranked as Eudragit-S100> DCP internal 1 used in pre-granulation or Mix stage> DCP internal 2 used in intra-granulation stage or GS-2> DCP external used in F-Mix stage > PVP internal used in extra-granulation stage.
Figure 6
Figure 6
Response surface plots of: (A) hardness: showing that desired hardness of less than 8 kg/cm2 was obtained by varying amount of Eudragit-S100 and DCP-Internal1. (B) Release at 2 h: showing the least effect of Eudragit-S 100 on release at 2 h (C) and (D) release at 3 h and 4 h: showing that Eudragit-S100 and DCP Internal 1 did not impart a significant effect on drug release at 3 h and 4 h. (E) and (F) release at 5 h and 6 h: showing the least effect of DCP-Internal 1 on drug release at 5 h and 6 h. (G, H) Release at 7 h and 8 h: showing the maximum amount of drug was released with the higher amount of Eudragit-S100 and minimum amount of DCP-Internal 1 at 7 h and 8 h.
Figure 7
Figure 7
FTIR spectra. (A) Mesalamine chemical structure. (B) Mesalamine FTIR peaks showing the –NH2 functional group bending peak and C=O functional group stretching at 1615–1700 cm−1, along with C-O stretch at 1215 cm−1. (C) FTIR spectra of (a) mesalamine; (b) mesalamine granules; (c) mesalamine tablet showing characteristic peaks of mesalamine functional groups in spectra of mesalamine, mesalamine matrix tablets, and granules with indication of no excipient-drug incompatibility.
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References

    1. Cuffari C, Pierce D, Korczowski B, et al. Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis. Drug Des Devel Ther. 2016;10:593. doi:10.2147/DDDT.S95316 - DOI - PMC - PubMed
    1. Perrotta C, Pellegrino P, Moroni E, et al. Five-aminosalicylic acid: an update for the reappraisal of an old drug. Gastroenterol Res Pract. 2015;2015:9. doi:10.1155/2015/456895 - DOI - PMC - PubMed
    1. Pierce D, Corcoran M, Martin P, et al. Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin xr, metronidazole, and sulfamethoxazole: results from four randomized clinical trials. Drug Des Devel Ther. 2014;8:529. doi:10.2147/DDDT.S55373 - DOI - PMC - PubMed
    1. Khan AM, Bashir S, Hanif M, Abbas N, Ahsan M. Colon specific formulation of mesalamine: preparation and in vitro evaluation. Lat Am J Pharm. 2016;35(6):1391–1398.
    1. Jin L, Ding Y-C, Zhang Y, Xu X-Q, Cao Q. A novel pH–enzyme-dependent mesalamine colon-specific delivery system. Drug Des Devel Ther. 2016;10:2021. - PMC - PubMed
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