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Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension

[ Vol. 21 , Issue. 40 ]

Author(s):

Aparna Saigal, Wai Kiong Ng, Reginald B.H. Tan and Sui Yung Chan   Pages 5868 - 5876 ( 9 )

Abstract:


Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million.

The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance.

Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product.

Keywords:

Pulmonary arterial hypertension, treatment, inhalation, controlled release, polymeric microspheres.

Affiliation:

Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.



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