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1.
J Pharm Sci ; 102(11): 4057-64, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23983168

ABSTRACT

The treatment of benign prostatic hyperplasia can be accomplished by the use of different drugs including, doxazosin, an α-1 adrenergic antagonist, and finasteride (FIN), a 5-α reductase inhibitor. Traditionally, treatments using these drugs have been administered as either a mono or combination therapy by the oral route. A transdermal delivery system optimized for doxazosin and FIN combination therapy would provide increased patient adherence and facilitate dose adjustment. Doxazosin base (DB) was prepared from doxazosin mesylate and characterized together with FIN, by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). The permeation enhancers, azone and lauric acid, and the gelling agents, hydroxypropyl cellulose (HPC) and Poloxamer 407 (P407), were evaluated to determine their ability to promote in vitro permeation of drugs through the pig ear epidermis. Successful preparation of DB was confirmed by evaluating the XRD, DSC, and NMR patterns and in vitro studies revealed that 3% (w/w) azone was the best permeation enhancer. When P407 gel was compared with HPC gel, it showed reduced lag time and promoted higher permeation of both drugs. This may be because of the interactions of the former with the stratum corneum, which disorganizes the lipid structure and consequently promotes higher drug permeation.


Subject(s)
5-alpha Reductase Inhibitors/administration & dosage , Adrenergic alpha-1 Receptor Antagonists/administration & dosage , Doxazosin/administration & dosage , Finasteride/administration & dosage , Pharmaceutical Vehicles/metabolism , 5-alpha Reductase Inhibitors/pharmacokinetics , Administration, Cutaneous , Adrenergic alpha-1 Receptor Antagonists/pharmacokinetics , Animals , Azepines/metabolism , Doxazosin/pharmacokinetics , Finasteride/pharmacokinetics , Humans , Lauric Acids/metabolism , Male , Permeability , Prostatic Hyperplasia/drug therapy , Skin Absorption , Swine
2.
Int J Nanomedicine ; 6: 2581-90, 2011.
Article in English | MEDLINE | ID: mdl-22114490

ABSTRACT

BACKGROUND: Diseases that affect the buccal cavity are a public health concern nowadays. Chlorhexidine and nystatin are the most commonly used drugs for the control of buccal affections. In the search for more effective antimicrobials, nanotechnology can be successfully used to improve the physical chemical properties of drugs whilst avoiding the undesirable side effects associated with its use. Herein described are studies using nystatin and chlorhexidine with sodium montmorillonite (MMTNa), and chlorhexidine with ß-cyclodextrin and two derivatives methyl-ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin in the development of antimicrobial nanosystems. METHODS: The nanosystems were prepared by kneading and solubilization followed by freeze-drying technique. The nanosystems were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Nanosystem antimicrobial activity against Streptococcus mutans and Candida albicans strains was evaluated with inhibition halo analysis. RESULTS: The nanocarriers MMTNa and cyclodextrins showed good yields. XRPD, FTIR, and DSC analysis confirmed the proposed nanosystems formation and the suitability of the production methods. The nanosystems that showed best antimicrobial effect were chlorhexidine gluconate (CHX) and cyclodextrin inclusion complexes and CHX:MMTNa 60% cation exchange capacity - 24 hours. CONCLUSION: The nanosystem formulations present higher stability for all chlorhexidine inclusion complexes compared with pure chlorhexidine. The nystatin nanosystems have the potential to mask the bitter taste, justifying subsequent in-vivo studies. For these reasons, further studies are being carried out to evaluate their application in professional formulations.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Candida albicans/drug effects , Mouth Diseases/prevention & control , Nanoparticles/chemistry , Streptococcal Infections/prevention & control , Streptococcus mutans/drug effects , Bentonite/chemistry , Calorimetry, Differential Scanning , Cations/chemistry , Chemistry, Pharmaceutical , Chlorhexidine/analogs & derivatives , Chlorhexidine/chemistry , Chlorhexidine/pharmacology , Freeze Drying , Mouth Diseases/microbiology , Nystatin/chemistry , Nystatin/pharmacology , Spectroscopy, Fourier Transform Infrared , Streptococcal Infections/microbiology , X-Ray Diffraction , beta-Cyclodextrins/chemistry
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