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Development and Optimization of Dextromethorphan HBr-2-Hydroxy Propyl ß-Cyclodextrin Inclusion Complex Based Orally Disintegrating Tablets Using Response Surface Methodology

Adhikari, Saugat
http://rave.ohiolink.edu/etdc/view?acc_num=mco1470340367

Abstract Details

2016, Master of Science in Pharmaceutical Science (MSP), University of Toledo, Pharmaceutical Sciences (Industrial Pharmacy).
The focus of this present investigation was to access the utility of various characterization techniques in the evaluation of Dextromethorphan HBr (DXM HBr) inclusion complex with 2-Hydroxy propyl ß-cyclodextrin (2-HPßCD). This techniques confirms the formation of the inclusion complex and explores the mode of complexation between DXM HBr and 2-HPßCD. It also predicts the ability of 2-HPßCD to mask the bitter taste of DXM HBr and explain its taste masking mechanism. In aqueous solution, the inclusion complex was studied utilizing the phase solubility method. The solubility of DXM HBr increased as a function of 2-HPßCD concentration. The solubility profile was classified as AL type: indicating the formation of a 1:1 stoichiometric inclusion complex. In solid state, the inclusion complex was prepared using lyophilization (freeze drying technique) and characterized by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FT-IR), Scanning Electron Microscopy (SEM), powder X-ray Diffraction (pXRD), proton nuclear magnetic resonance (1HNMR) spectroscopy and 2D-NMR rotating Over Hauser effect spectroscopy (ROESY). FT-IR showed no interaction between DXM HBr and 2-HPßCD and confirmed the formation of the complex. DSC and SEM studies further confirmed the inclusion complex formation. pXRD analysis indicated that the crystallinity of the inclusion complex reduced significantly. NMR spectroscopy elucidated the mode of complex formation. The subsequent incorporation of the inclusion complex into orally disintegrating tablets (ODTs) was done to develop the formulation. This results in patient adherence and convenience and enhances the dissolution rate by rapid absorption of drug through oral mucosa. Response surface methodology with central composite design was employed in the optimization of the formulation factors, such as concentration of croscarmellose sodium (CCS) and microcrystalline cellulose (MCC), to obtain ODTs within the range of 3.5 to 5.5 kp hardness, 6.3 to 45 second disintegration time and 1.2 to 6.06 minutes mean dissolution time (MDT). The results indicated selected factors which have a strong influence on properties of the ODTs. The optimum concentration of CSS and MCC predicted by the model was 5.168 mg (2.5%) and 81.814 mg (40%), respectively for preparing a DXM HBr-2-HPßCD inclusion complex based ODT with a hardness of 4.5 kp, disintegration time of 10 seconds and MDT of 1.341 minutes. Thus, this approach exhibited the ability of masking the bitter taste of DXM HBr when complexed with 2-HPßCD, which resulted in ODTs formulations with improved patient adherence and acceptability.
Kenneth S. Alexander (Committee Chair)
Sai Hanuman Sagar Boddu (Committee Member)
Jerry Nesamony (Committee Member)
112 p.
Pharmaceuticals; Pharmacy Sciences
Dextromethorphan HBr, 2-hydroxy propyl beta-cyclodextrin, inclusion complex, orally disintegrating tablets, response surface methodology, central composite design

Recommended Citations

Citations

  • Adhikari, S. (2016). Development and Optimization of Dextromethorphan HBr-2-Hydroxy Propyl ß-Cyclodextrin Inclusion Complex Based Orally Disintegrating Tablets Using Response Surface Methodology [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1470340367

    APA Style (7th edition)

  • Adhikari, Saugat. Development and Optimization of Dextromethorphan HBr-2-Hydroxy Propyl ß-Cyclodextrin Inclusion Complex Based Orally Disintegrating Tablets Using Response Surface Methodology. 2016. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1470340367.

    MLA Style (8th edition)

  • Adhikari, Saugat. "Development and Optimization of Dextromethorphan HBr-2-Hydroxy Propyl ß-Cyclodextrin Inclusion Complex Based Orally Disintegrating Tablets Using Response Surface Methodology." Master's thesis, University of Toledo, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=mco1470340367

    Chicago Manual of Style (17th edition)

mco1470340367
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© 2016, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.