Role of humic acid on oral drug delivery of an antiepileptic drug.
BACKGROUND
Humic acid (HA) is omnipresent in natural organic matter that is a macromolecular, negatively charged polyelectrolyte that contains a hydrophobic core. It is also present in a significant amount in Shilajit (used frequently in traditional medicines), which is used in this study as a source of extraction. HA is evaluated for the oral drug delivery of carbamazepine (CBZ).


OBJECTIVE
HA is used in this study to increase the dissolution, intestinal permeation, and pharmacodynamic response of CBZ (bio pharmaceutics classification system (BCS) II) by the technique of complexation and other related mechanism reported with humic substances.


METHODS
Different complexation techniques were explored in this study for the entrapment of CBZ, which was authenticated by molecular modeling and conformational analysis. These were further characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Solubility analysis and dissolution release profile were carried out to access the in vitro parameters. For ex vivo studies, rat gut intestinal permeability was done. And finally pharmacodynamic evaluation (maximal electroshock method) was carried out for optimized complexes.


RESULTS
Molecular modeling approach and instrumental analysis (DSC, XRD, and FT-IR) confirmed the entrapment of CBZ inside the complexing agent. Increased solubility (∼1742%), sustained release (∼78%), better permeability (∼3.5 times), and enhanced pharmacodynamic responses conferred the best to 1:2 freeze dried (FD) and then 1:2 kneading (KD) complexes compared with pure CBZ.


CONCLUSIONS
Now it could be concluded that HA may be tried as a complexing agent for antiepileptic drug and other classes of low water-soluble drug.
Mirza
Mohd Aamir
MA
Department of Pharmaceutics, Jamia Hamdard, New Delhi, India.
Agarwal
Suraj Prakash
SP
Rahman
Md Akhlaquer
MA
Rauf
Abdur
A
Ahmad
Niyaz
N
Alam
Aftab
A
Iqbal
Zeenat
Z
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004304:Dosage Forms; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005612:Freeze Drying; D006812:Humic Substances; D007583:Jejunum / Q000378:metabolism; D008968:Molecular Conformation; D010539:Permeability; D051381:Rats; D012995:Solubility
D000927:Anticonvulsants; D004304:Dosage Forms; D004337:Drug Carriers; D006812:Humic Substances; D002220:Carbamazepine