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Development of a cyclodextrin-based nasal delivery system for lorazepam.
1Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. mjug@pharma.hr
Drug Development and Industrial Pharmacy
|July 16, 2008
Summary
This study developed novel mucoadhesive microparticles for nasal drug delivery, enhancing lorazepam solubility and release using hydroxypropyl-beta-cyclodextrin (HP-beta-CD) inclusion complexes. The system improves drug solubility and nasal drug delivery efficacy.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Drug Delivery
Background:
- Nasal drug delivery faces challenges with poorly water-soluble drugs.
- Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) can improve drug solubility.
- Mucoadhesive polymers enhance drug residence time at the nasal mucosa.
Purpose of the Study:
- To develop and characterize mucoadhesive microparticles for nasal delivery of lorazepam.
- To investigate the role of HP-beta-CD inclusion complexes in improving drug solubility and release.
- To evaluate the impact of different mucoadhesive polymers on microparticle properties.
Main Methods:
- Spray drying was used to encapsulate lorazepam (free or as HP-beta-CD complex) into microparticles with hydroxypropylmethyl cellulose (HPMC), carbomer, or HPMC/carbomer interpolymer complex (IPC).
- Differential scanning calorimetry (DSC) analyzed drug crystallinity.
- Swelling rate, mucoadhesion, and in vitro dissolution studies were performed.
Main Results:
- IPC- and carbomer-based microparticles exhibited superior swelling and mucoadhesion compared to HPMC-based ones.
- Drug loading reduced swelling and mucoadhesion; HP-beta-CD inclusion complex formation did not further reduce these properties.
- Microparticles with lorazepam inclusion complexes showed 1.8-2.5 times faster in vitro drug release than those with free lorazepam.
Conclusions:
- Mucoadhesive microparticles formulated with HP-beta-CD inclusion complexes offer a promising system for nasal delivery of poorly soluble drugs like lorazepam.
- The choice of mucoadhesive polymer significantly influences microparticle swelling and mucoadhesion.
- HP-beta-CD complexation enhances lorazepam solubility and dissolution rate, improving potential nasal bioavailability.
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