Amoxicillin trihydrate

The β-lactam antibiotics is a class of bactericidal drugs having β-lactam ring in their molecular structure. Amoxicillin, an acid-stable, semi‐synthetic antibiotic belongs to a group of Penicillins. β-lactam antibiotics effectively inhibit the catalytic activity of bacterial transpeptidases. Hence these enzymes are also referred to as penicillin‐binding proteins (PBPs). The PBP-inhibitory activity of penicillin and other β-lactam antibiotics is due to the structural, geometric, and stereochemical similarities between the amide bonds of penicillin and the enzyme substrate (D-Ala-D-Ala dipeptide -2). The finding indicates that transpeptidase or penicillin-binding proteins (PBPs) is presumed to form a penicilloyl-enzyme complex, in the presence of β-lactam antibiotics which, for steric reasons, precludes addition of the amino terminus of the pentaglycine unit, resulting in the reaction (transpeptidase-catalyzed deacetylation reaction) being aborted. This reaction defines the irreversible nature of enzyme inhibition, which is achieved through the nucleophilic addition of serine residue present at the active site to the carbonyl group of the β-lactam ring. The end result is the inactivation of transpeptidase, a characteristic that significantly weakens the cross-linking of peptidoglycan. The weakening of peptidoglycan results in bacterial cells becoming highly prone to lysis and death at their growth phase. This is the reason why β-lactam antibiotics are referred to as bactericidal agents.

Fig. 1 Differences in the Molecular Structures of Amoxicillin and Penicillin G. (Lima LM.; et al. 2020)

The high-dose oral administration of amoxicillin is one of the treatment methods for acute bacterial sinusitis, however, this method can increase the risk of systemic side effects and antibiotic resistance. Nasal administration is a new potential and promising method of drug delivery. Nasal administration has many advantages such as nasal delivery, easy administration, and patient compliance, however, mucociliary clearance (MCC) in the nasal cavity that has a protective role as a cleaning agent of foreign substances has been a major problem in research of nasal administration of drugs. In an effort to develop amoxicillin as a local drug for the nasal cavity to effectively treat acute bacterial sinusitis, the Mardikasari SA research team formulated an in situ ionic-sensitive polymer form of amoxicillin. This formulation will make amoxicillin stick to the mucosa of the nasal cavity without penetrating it, so it can increase the effectiveness of local administration.

Fig. 2 Preparation of mucoadhesive In Situ Nasal Gel of Amoxicillin Trihydrate and investigations on local applicability. (Mardikasari SA.; et al. 2024)