Pharmacokinetic evaluation of quetiapine fumarate controlled release hybrid hydrogel: a healthier treatment of schizophrenia

Abstract

The current study aimed to rationally develop and characterize pH-sensitive controlled release hydrogels by graft polymerization of gelatin (Gel) and hydroxypropyl methyl cellulose (HPMC) in the presence of glutaraldehyde (GA) using quetiapine fumarate for the treatment of schizophrenia. The prepared hydrogels discs were subjected to various physicochemical studies including: swelling, diffusion, porosity, sol-gel analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Three different pH values (1.2, 6.8 and 7.4) were used to determine shape, transition, and controlled release behavior of prepared hydrogels. Various kinetic models including zero order, first order, Higuchi model and Power Law equation were applied on drug release data. The optimized hydrogels were subjected to in vivo studies using albino rabbits. Swelling and release results were found to be insignificant (p < .05) evidencing that there was no significant difference in swelling and drug release rate of hydrogels in different pH mediums. Swelling, porosity, gel-fraction, and drug released (%) were found to be dependent on concentrations of Gel, HPMC, and GA. Kinetic models revealed that QTP-F release followed non-Fickian diffusion. In-vivo studies contributed significantly higher plasma QTP-F concentration (C max), time for maximum plasma concentration (T max), area under the curve (AUC0–inf) and half-life (t 1/2) as 18.32 ± 0.50 µg/ml, 8.00 ± 0.01 hrs, 6021.2 ± 5.09 µg.hrs/ml and 10.06 ± 0.43 hrs, respectively, for test-hydrogels when compared to reference market brand (Qusel® 200 mg, Hilton Pharma, Karachi, Pakistan) QTP-F tablets. It might be concluded that QTP-F loaded pH-sensitive hydrogels were developed successfully with reduced dosing frequency for schizophrenia.

pH‐Responsive Studies of Bacterial Cellulose /Chitosan Hydrogels Crosslinked with Genipin: Swelling and Drug Release Behaviour

“…QF is an antipsychotic drug for treating schizophrenia and the chemical structure is shown in Figure . QF is administered twice a day and the problem of patients skipping doses has been reported in most cases . Hence, the need for a delivery system for QF that could offers extended release (ER), minimize side effects due to over‐dosage with improve compliance in schizophrenia patients and in which QF does not have any chemical interactions with the hydrogel matrix.…”

Targeted Delivery of Methotrexate through pH-sensitive Hydrogel: To Treat Colon Pathology

“…After taking results of all the samples, it was observed that by increasing the concentration of the PVA, the % gel fraction was increased and vice versa [41]. By increasing the polymer 'gelatin' concentration, there can be occur an increase in the % gel fraction and decrease in the sol fraction [28]. Adding or increasing concentration of glutaraldehyde in the formulations may also results in increasing of the % gel fraction, because cross-linker will cause increase entanglement of the more polymer chains of the gel formulation [42].…”

“…ANOVA and t-test were also applied. P-values occurred less than 0.01 of a result were considered of significant difference [28].…”

“…The peaks of gelatin polymer shown in the FTIR spectra indicate the following chemical groups. The peak occurs at 3284 cm -1 indicate the stretching of -N-H group of secondary amides, the peak occur at 2932 cm -1 indicates C-H stretching group, the peak of 1631.3 cm -1 indicates the stretching of C=O, amide I, and C-N stretching groups, the peak at 1530 cm -1 indicate -N-H bending, the peak at 1237.6 cm -1 indicate the amide -III [28] as shown in figure 3(p). The FTIR spectra of the pure PVA shown a peak of broad band at 3320.74 cm -1 is belong to the O-H stretching groups which occur due to inter and intra molecular hydrogen bond.…”

“…The purpose of drug targeting to the desired organ system (area) of the body is not to deliver a drug only for increasing its therapeutic effects there, but also to lower its toxic effects in low dose range during that therapy [26] and improve the efficacy and reduce the side effects [27]. Due to various reasons the drug targeting to specific organ or tissue is required, such as to save/protect the drug moiety from the harsh environment, to minimize the adverse effect and improve the therapeutic effect of the drug in that targeted organ and to protect also the other organs or tissues from the harmful/adverse effect of that targeted drug substance [28].…”