Abstract
Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100(r) solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the enteric-coated pellets. Acrycoat L 100(r) was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH.
Highlights
Tuberculosis is one of the most common causes of infectious, disease-related mortality worldwide
Multidrug-resistant tuberculosis remains the main cause of death among patients with human immunodeficiency virus (HIV) (World Health Organization (WHO), 2011)
The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease recommend the use of fixed doses of the firstline drugs for tuberculosis treatment: rifampicin (RMP), isoniazid, (INH) pyrazinamide (PYR) and ethambutol (ETH) in order to assure adequate treatment (WHO, 2011)
Summary
Tuberculosis is one of the most common causes of infectious, disease-related mortality worldwide. Factors such as lack of patient compliance to the treatment regimen (which can take up to 9 months), development of multiresistant microorganisms and co-infection with the human immunodeficiency virus (HIV) have contributed to the failure of medical treatment and to increased mortality rates. RMP undergoes hydrolysis in an acid pH leading to 3-formylrifamycin (3-FRSV), which is poorly absorbed. This compound reacts with INH forming isonicotinyl hydrazone (HYD). The dose available for absorption is significantly decreased (Shishoo et al, 1999; Singh et al, 2000, 2001)
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