Sustained Release Bilayer Tablet of Ibuprofen and Phenylephrine Hydrochloride: Preparation and Pharmacokinetics in Beagle Dogs

Abstract

Cold is a global common infectious disease accompanied by symptoms such as headache and stuffy nose. Ibuprofen (IBU) and phenylephrine hydrochloride (PE) were commonly used for common cold due to their different effects in relieving fever and the main symptoms such as nasal congestion and high sinus pressure. However, the commercial tablets of IBU and PE have to be administered 2 to 3 times per day due to their short half-life, with inconvenience for patient and fluctuations of plasma concentration. Bilayer tablet technology was utilized to design the IBU-PE sustained release tablets because of the significantly different solubility of IBU and PE in release media. The formulations of IBU layer and PE layer contain different viscosity grades of hydroxypropyl methylcellulose (HPMC) as sustained-release matrix, hydrophilic diluent, and traditional glidant and lubricant. The sustained release bilayer tablet exhibited satisfying sustained release performance with the mechanisms of diffusion and matrix erosion. Compared with the conventional tablets, the IBU-PE sustained release bilayer tablet expressed significantly sustained-release behavior with decreased C max and prolonged T max in fasted conditions for IBU and PE. Though IBU of IBU-PE sustained release bilayer tablet was bioequivalent to the commercial IBU tablet, the relative bioavailability of PE from the bilayer tablets was 87.49 ± 20.00% (90% confidence interval was 72.3 to 102.5%), indicating bioinequivalence probably due to the Bfirst pass^effect.

Hydroxypropyl cellulose/Polyvinylpyrrolidone Matrix Tablets Containing Ibuprofen: Infiltration, Erosion and Drug Release Characteristics

“…[5,6] It is the oldest drug of the propionic acid group [7] and belongs to nonsteroidal anti-inflammatory drugs (NSAIDs). [4,[7][8][9][10][11] It is accepted as one of the safest NSAIDs [11,12] and is widely used in the worldwide. [7,13] Ibuprofen is preferred as a model drug for sustained [8,14,15] and controlled drug delivery systems [14] due to its good pharmacological efficiency, [14,15] short half-life (2 h) [8,14] and appropriate molecule size changing between 1.0-0.6 nm.…”

“…Ibuprofen, [2‐(4‐isobutylphenyl) propionic acid], is extensively used for the treatment of rheumatoid diseases [1–3] and to reduce pain, [2,4,5] fever [6] and inflammation [5,6] . It is the oldest drug of the propionic acid group [7] and belongs to nonsteroidal anti‐inflammatory drugs (NSAIDs) [4,7–11] . It is accepted as one of the safest NSAIDs [11,12] and is widely used in the worldwide [7,13] .…”

Bilayer Tablet Tendered Immediate Release of Paracetamol and Sustained Release of Ibuprofen for Quick Onset of Action Against Pain and Fever

“…Bi-layer tablets can be primary option to avoid chemical incompatibilities between APIs by physical separation and to enable the development of different drug release profiles. Bi-layer tablets are novel drug delivery systems where a combination of two or more drugs in a single unit [10,11]. Bi-layer tablet is suitable for sequential release of two drugs in combination in which one layer is for immediate release and second layer is sustained release.…”