Bioequivalence of Orally Inhaled Drug Products : Focus on Current Regulatory Perspectives.

Asthma/chronic obstructive pulmonary disease (COPD) medication market is a fast growing market, especially in the emerging markets where drugs have not been launched due to high costs. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Orally inhaled products (OIPs) should continue to remain an attractive clinical proposition. At the same time, establishing bioequivalence of an inhaled therapeutic can be a challenging proposition. The purpose of establishing bioequivalence is to demonstrate equivalence between the generic medicine and the originator medicine in order to allow bridging of the pre-clinical and clinical testing performed on the originator drug. Methodologies to determine bioequivalence are well established for oral, systemically acting formulations. However, for inhaled drugs, there is currently no universally adopted methodology, and regulatory guidance in this area has been subject to debate. There is no one-size-fits-all programme. This review article mainly focused on current regulatory perspectives on bioequivalence of topically acting, orally inhaled drug products.

Comparative Efficacy of Generic Salmeterol Xinafoate/Fluticasone Propionate MDI Fixed Dose Combination and Seretide ® MDI in Asthmatic Patients: An Open Label, Randomized, Phase III Study.

The addition of an inhaled long-acting β2-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients. The long-acting β2-agonist (LABA) Salmeterol xinafoate (Salmeterol) and inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) are being made available as a combination product Seretide® pMDI (Salmeterol/ Fluticasone) in a single aerosol inhaler. This randomized, open label, non-inferior, multicentric, 12-week, phase III study compared the efficacy and safety of generic Salmeterol/Fluticasone with commercially available product Seretide®. Materials and methods:Patients aged > 12 years inclusive of either sex (N = 372) with persistent asthma as defined by NHLBI for > 6 months prior to screening were included in the study. After a screening phase (1 week), eligible patients were enrolled in the trial with 2 weeks run in period. Eligible patients were randomized to receive either of the two treatment groups [HFA-Propelled pMDI Salmeterol/Fluticasone (25/250mcg) or HFA-Propelled Seretide® (25/250mcg) pMDI] in a ratio of 1:1 for the 12- week treatment period. The primary objective was to demonstrate non-inferiority of Salmeterol/Fluticasone versus Seretide®, measured by mean pre-dose forced expiratory volume in the first second (FEV1), at week 12. Results: This study provides evidence for the primary efficacy endpoint that Salmeterol/Fluticasone was statistically as well as clinically non-inferior to Seretide® in the treatment of patients with persistent asthma. This was supported by secondary endpoints which demonstrate that Salmeterol/Fluticasone appeared to be comparable to Seretide® in terms of efficacy for the secondary efficacy endpoints (morning PEFR, evening PEFR, diurnal variability of PEFR, daytime and night-time asthma symptoms score, average need for short acting-β2-agonists, proportion of patients that required rescue medication, patients with nocturnal asthma, patients without asthma symptoms of score 0 and average number of days without asthma symptoms of score 0). Salmeterol/Fluticasone was safe and well tolerated; and safety profile is comparable to comparator Seretide®. Conclusion: The results of study demonstrate that generic and innovator HFA formulations of Salmeterol/Fluticasone are clinically interchangeable. Overall, the study indicates that HFA-Propelled Salmeterol/ Fluticasone (25/250mcg) pMDI was safe, well tolerated and non-inferior in efficacy compared to HFA-Propelled Seretide® (25/250mcg) pMDI.

Antiulcer activity of Garcinia indica linn fruit rinds.

Garcinia indica Linn (Clusiaceae), a medicinal plant mentioned in Ayurveda has been used for treatment of liver disorders, dysentery, sunstroke, cancer and heart diseases. The present study was undertaken to investigate ulcer protective effect of aqueous and ethanolic extract of Garcinia indica Linn fruit rind. The aqueous and ethanol extract of Garcinia indica Linn were investigated for ulcer protective activity against indomethacin induced ulcerogenesis and HCl/ethanol induced gastric lesion. Oral administration of the aqueous and ethanol extracts of Garcinia indica fruit rind at the dose 500 mg/kg provided significant (p<0.001) reduction of ulcer index in the HCl/ethanol and indomethacin induced gastric lesion rat models.