Propranolol Micro Particle Production by Spray Drying Technique and Evaluation of the In Vitro and In Vivo Lung Deposition

Abolghasem Safdar,Mohammad Ali Darbandi

doi:10.21767/2471-8157.100023

Abolghasem Safdar, Mohammad Ali Darbandi

Open Access

https://doi.org/10.21767/2471-8157.100023

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Abstract

The goal of this study is to prepare the inhalable micro particles from propranolol by spray drying method. Prescription of propranolol by the oral rout of administration suffers from the hepatic first pass metabolism effect. This phenomenon caused to decrease the oral bioavailability of the propranolol. It is possible to eliminate the hepatic first pass metabolism effect by prescription of the propranolol inhalable micro particles via the pulmonary system. The different solvent as the spray drying vehicle such as water and the mixture of the water and ethanol were applied for preparation of the propranolol inhalable micro particles during the spray drying process. The physical characteristics of the micro particles such as true and bulk density, size, shape and aerodynamic behavior of the particles were evaluated by the in vitro test. In the in vivo tests the inhalable microparticles were insufflated to the lung of the rats. The plasma samples 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8 hours after insufflation of the drug to the lung of the animal, intravenous and oral administration of drug were collected. The concentration of propranolol in the plasma samples were measured by the HPLC method. The pharmacokinetic parameters of the drug such as AUC0-60, Tmax, Cmax, T1/2, Ke, Ka, Vd and absolute bioavailability of drug were calculated. The results of the in vitro tests showed that the type of the spray drying vehicle has the significant effect on the physical characteristics and the aerodynamic behavior of the propranolol inhalable micro particles. The presence of 75% ethanol in the spray drying vehicle caused to increase in fine particle fraction. The value of the fine particle fraction for these micro particles was ±35.771. The results of the in vivo tests showed that the rate and extent of the pulmonary absorption of propranolol is more than the oral rout of administration. The presences of the different excipients in the spray drying vehicle and the type of the spray drying vehicle have the significant effect on the pulmonary absorption of the drug. It is possible to reach 0.69+0.27 as the value of the absolute bioavailability by prescribing the propranolol via the pulmonary system. Keywords: Fine particle fraction; Aerodynamic behavior; Propranolol; Ethanol; Pulmonary absorption-propranololinhalable microparticles-absolute bioavailability

Highlights

The advantages of lung as the respiratory organ such as high level of the blood flow rate, the permeability of the capillary, the wide surface for absorption of drugs and the low level of peptidase enzyme in compare with the gastrointestinal system make it the suitable organ for delivering of drugs to the systemic circulation [1,2]
3 mg of drug as the powder was introduced into the lung through the obtuse syringe which was connected through the tracheal cannula to a depth of 2.5 cm below the tracheal incision
We examined the effect of various spray drying propranolol single dose 3 mg was administered via intra tracheal, intravenous and oral rout to healthy rats and the plasma concentration of propranolol was measured

Summary

Introduction

The advantages of lung as the respiratory organ such as high level of the blood flow rate, the permeability of the capillary, the wide surface for absorption of drugs and the low level of peptidase enzyme in compare with the gastrointestinal system make it the suitable organ for delivering of drugs to the systemic circulation [1,2]. Respiratory drug delivery has many advantages include eliminating the hepatic first pass metabolism effect and delivering of the impermeable macromolecules such as amino glycosides to the blood circulation [3]. These advantages cause to apply from this rout as the alternative for the oral and the parenteral rout of administration for peptide and proteins [4,5,6,7,8]. There are three types of inhalable dosage forms include nebulizer solutions, pressurized metered dose inhalers (PMDI) and dry powder inhalers (DPI) for respiratory drug delivery [9,10,11] Among these types of dosage forms DPIs as the solid pharmaceutical dosage forms are more stable than the others. Lactose is applied as the vehicle in most of the DPI formulations [13,14]

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