Dissertation
Bioadhesive systems targeting the buccal and esophageal mucosa to improve site specific delivery
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2021
DOI: 10.17077/etd.006108
Abstract
One of the major limitations to transmucosal drug delivery is the lack of retention of the dosage forms at the administration site. Bioadhesive delivery systems increase the residence time/retention of the dosage form at the application site, and these studies focused on the development of bioadhesive dosage forms for application to the buccal mucosa or to the esophagus.A bioadhesive thin-film system containing midazolam was designed and evaluated to assess the suitability of buccally-delivered midazolam for emergency seizure conditions. Hydroxypropyl methylcellulose (HPMC E4M), polyvinyl pyrrolidine (PVPK-90), and Kollicoat®-IR (polyvinylpyrolidine + PEG) were evaluated as mucoadhesive and film-forming polymers. Films containing a permeation enhancer, 5% sodium caprylate, showed good midazolam absorption across excised porcine buccal tissues, and when an additional permeation enhancer, l-menthol, was incorporated into the film improved midazolam flux was observed. Further evaluation of the direct effects of these permeation enhancers on the buccal mucosa using electron spin resonance study showed that both l-menthol and sodium caprylate acted to fluidize lipid bilayers with the permeation enhancers interacting both in the polar regions and the inner acyl regions of bilayers resulting in increasing midazolam permeability across the mucosal tissue barrier.
Bioadhesive systems suitable for targeted esophageal delivery were also investigated. Various bioadhesive vehicles were screened for their mucoretention and gelation behaviors in the presence of saliva and on the surface of excised esopahgeal tissues. Several ion-sensitive polymers including gellan gum, xanthan gum and sodium alginate exhibited ~80-90% mucoretention of the gel formulation on an in vitro esophageal tissue model. Confocal microscopy confirmed that the ion-sensitive polymer gels were retained on the tissue surface for at least 30 min, even under conditions with frequent washing with artificial saliva. Tissue accumulation studies from gels loaded with ciclesonide, an anti-inflammatory pro-drug compound, showed that at least 15µg/g of active drug (des-ciclesonide) accumulated within the esophageal tissues following a 30 min gel formulation application period. These bioadhesive gel formulations had sufficiently low viscosity to allow for easy swallowing but rapidly formed a bioadhesive gel following exposure to saliva. Properly formulated bioadhesive systems show great promise for the improved delivey of drugs via a number of mucosal deliver sites. Careful selection of bioadhesives and active excipients can improve the absorption of drugs into and through mucosal tissues resulting in improved local or systemic delivery.
Details
- Title: Subtitle
- Bioadhesive systems targeting the buccal and esophageal mucosa to improve site specific delivery
- Creators
- Laxmi Shanthi Chede
- Contributors
- Maureen Donovan (Advisor)Alisager K Salem (Committee Member)Nicole K Brogden (Committee Member)Philip Wertz (Committee Member)Riad Rahhal (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Pharmacy
- Date degree season
- Spring 2021
- DOI
- 10.17077/etd.006108
- Publisher
- University of Iowa
- Number of pages
- xviii, 166 pages
- Copyright
- Copyright 2021 Laxmi Shanthi Chede
- Language
- English
- Description illustrations
- illustrations (some color)
- Description bibliographic
- Includes bibliographical references.
- Public Abstract (ETD)
One of the major limitations to drug delivery at mucosal administration sites is the limited retention of the dose at the tissue surface. Bioadhesive delivery systems increase the residence time/retention of the dosage form at the application site, and the studies undertaken in this research project focused on the development of bioadhesive dosage forms for application to the buccal and esophageal tissues. To retain the drug at the site of administration for improved absorption and ease of administration, thin-film delivery systems were prepared and evaluated for improved midazolam permeation . The addition of permeation enhancers to the bioadhesive thin film containing midazolam resulted in greater amounts of midazolam being absorbed through the buccal mucosa.
Bioadhesive gel formulations which have low viscosities for easy swallowing but rapidly gel in the presence of salivary ions were found to be promising vehicles for use in the direct treatment of esophageal conditions. These gels were able to resist dilution and clearance from salivary washing and were able to deliver ciclesonide, an anti-inflammatory medication, to provide a therapeutically effective concentration of the active form of the drug in test esophageal tissues.
- Academic Unit
- Pharmacy; Craniofacial Anomalies Research Center
- Record Identifier
- 9984097170902771
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