Corresponding author (Pharmaceutics and Drug Delivery): Iman Taha, itaha@go.olemiss.eduhttps://egrove.olemiss.edu/pharm_annual_posters_2022/1020/thumbnail.jp

Ashour, Eman A.

ElSohly, Mahmoud A.

Omari, Sundus H.

Radwan, Mohamed M.

Repka, Michael A.

Taha, Iman

English

eGrove (Univ. of Mississippi)

University of Mississippi eGrove Annual Poster Session 2022 Annual Poster Session 10-11-2022 Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD) Iman Taha University of Mississippi, itaha@go.olemiss.edu Mahmoud A. ElSohly University of Mississippi Mohamed M. Radwan University of Mississippi Sundus H. Omari University of Mississippi Michael A. Repka University of Mississippi See next page for additional authors Follow this and additional works at: https://egrove.olemiss.edu/pharm_annual_posters_2022 Recommended Citation Taha, Iman; ElSohly, Mahmoud A.; Radwan, Mohamed M.; Omari, Sundus H.; Repka, Michael A.; and Ashour, Eman A., "Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD)" (2022). Annual Poster Session 2022. 21. https://egrove.olemiss.edu/pharm_annual_posters_2022/21 This Book is brought to you for free and open access by the Annual Poster Session at eGrove. It has been accepted for inclusion in Annual Poster Session 2022 by an authorized administrator of eGrove. For more information, please contact egrove@olemiss.edu. Authors Iman Taha, Mahmoud A. ElSohly, Mohamed M. Radwan, Sundus H. Omari, Michael A. Repka, and Eman A. Ashour This book is available at eGrove: https://egrove.olemiss.edu/pharm_annual_posters_2022/21 REFERENCESEmploying Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD) Iman E. Taha1, Mahmoud A. ElSohly 1,2 , Mohamed M. Radwan2, Sundus H. Omari1, Michael A. Repka 1,3, Eman A. Ashour11Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA. 2National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA. 3Pii Center for Pharmaceutical Technology, University of Mississippi, University, MS 38677, USA. RESULTSPURPOSECannabidiol (CBD) is a non-psychoactive cannabinoid isolatedfrom Cannabis sativa. It has been reported that CBD hasanticonvulsant, anxiolytic, antipsychotic, and anti-inflammatoryeffects and was approved by the FDA as a treatment ofepilepsy in pediatric. Despite the many pharmacologicalpotentials of CBD, its drawbacks have limited its applicationsin therapeutics. Poor water solubility is the major drawback inaddition to the first-pass metabolism and thus lowbioavailability (approximately 6%). The primary purpose of thecurrent project was to enhance the CBD bioavailability byimproving its solubility and avoid the effect of first-passmetabolism using Hot-Melt Extrusion technology.CONCLUSIONSuccessfully mucoadhesivebuccal films have beendeveloped using HMEtechnology. The results of thisstudy showed an enhancementof the solubility and drug releaseof CBD. This finding supportsthat the developed formulationspromise to enhance the CBDbioavailability.METHODSDifferent formulations were developed by mixing 10% w/wCBD with polymeric carrier/s and other excipients (Table 1).The resulted physical mixtures were fed into a ThermoScientific HAAKE Mini lab II (Thermo Fisher Scientific) and afilm die (1 mm thickness) was used to produce the CBD films.Differential scanning calorimetry DSC (TA DSC 25) wasperformed for CBD, the polymeric carriers and the extrudedfilms to determine their thermal characterization. Sampleswere weighed in T-zero pans (3–5 mg). The temperature waselevated from 25 to 200 °C at a rate of 10 °C/min under a flowof ultrahigh purity nitrogen gas. CBD drug content and contentuniformity were evaluated by HPLC. Bio-adhesion test wasperformed using a texture analyzer (TA-XT2) to evaluate theadhesiveness properties of each film. Solubility studies wereperformed for the developed films and the pure CBD using theshake-flask method at room temperature for 48 hours toevaluate the improvement of CBD solubility in the HME films.A drug release study was performed using a multi-positionStirring Hot Plate. The dissolution media used was 100 mL ofsimulated saliva (pH 6.8), 0.1 % w/v SLS at 37 ± 0.5 ºC.Samples withdrawal were at 15, 30, 60, 90, 120, 180 and 240minutes for analysis using HPLC.OBJECTIVEThe main objective of this project was to develop CBD muco-adhesive buccal film using HME in order to improve the watersolubility, avoid the first pass metabolism and thereforeenhance the CBD bioavailability. The drug content in all the formulations was in the range of 93.6 - 103%. The DSC results show melting peaks at 69 ºC and 65 ºC for CBD andPEO N80 respectively. The CBD endothermic peak disappeared in allprepared HME films indicating the transformation of CBD from crystallineto amorphous state (Figure 1). The bio-adhesion results (Table 2) demonstrated higher adhesivenes.sfor the formulation containing PEO N80 and carbopol compared to otherformulations. The solubility studies showed an enhancement in CBD solubility for allHME buccal films (Figure 2). The CBD water solubility showed 125.60,307.56, 318.22, and 362.72 µg/mL for formulations F4, F6, F7, and F8respectively. While the pure CBD water solubility was below the LOD ofthe analytical method. The drug release studies, as shown in Figure 3 showed significantenhancement in the CBD release in formulations F4, F6, F7 and F8 (2 to5 fold) compared to the pure CBD.peak forceNAdhesivenessN.mmwork of adhesion StringinessmmF1 0.774 1.095 0.183 0.412F2 0.670 0.726 0.061 0.221F3 0.839 0.977 0.131 0.276F4 0.565 0.781 0.078 0.208F5 0.221 1.060 0.034 0.182F6 0.846 1.663 0.258 0.512F7 1.276 1.607 0.423 0.591F8 0.944 1.126 0.320 0.637PEO-N80 % w/wKlucelTMEF % w/wSOLUPLUS % w/wTPGS % w/wSLS% w/wCBD% w/wCarbopol980% w/wCarbopol934% w/wF1 68 0 10 0 2 10 0 10F2 75 0 10 5 0 10 0 0F3 0 75 10 5 0 10 0 0F4 0 68 10 10 2 10 0 0F5 30 38 10 10 2 10 0 0F6 75 0 0 5 0 10 10 0F7 75 0 0 5 0 10 0 10F8 85 0 0 5 0 10 0 0• Moltke J, Hindocha C. Reasons for cannabidiol use: a cross-sectional study of CBD users, focusingon self-perceived stress, anxiety, and sleep problems. Journal of cannabis research. 2021Dec;3(1):1-2.• Mannila J, Järvinen T, Järvinen K, Jarho P. Precipitation complexation method producescannabidiol/β-cyclodextrin inclusion complex suitable for sublingual administration of cannabidiol.Journal of pharmaceutical sciences. 2007 Feb 1;96(2):312-9.• Langley N, DiNunzio J, Repka MA. Melt Extrusion: Materials, Technology and Drug Product Design(AAPS Advances in the Pharmaceutical Sciences Series). Springer; 2013.• Thakkar R, Thakkar R, Pillai A, Ashour EA, Repka MA. Systematic screeningof pharmaceutical polymers for hot melt extrusion processing: A comprehensivereview. International journal of pharmaceutics. 2020 Feb 25;576:118989Table 1. HME buccal film formulation compositionFigure 3. release study profiles for f4, f6, f7 and f8 and pure CBDFigure 1. DSC Thermogram of CBD, polymers, and HME films (F1, F2, F3, F4, F5, F6, F7, and F8)Figure 2. CBD water solubility in µg/mL for F4, F6, F7,F8, and pure CBD.Table. 2 Ex-vivo adhesion results for CBD mucoadhesive buccal films

Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD)

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Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD)

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