Comparative study between simple and optimized liposomal dispersion of quetiapine fumarate for diffusion through nasal route

Abstract

Context: Nasal route of drug administration is preferred more and more for the targeted delivery to the brain in current drug development scenario due to its ease of use, reliability, quick action, and lesser side effects. Those CNS drugs which have limited oral bioavailability due to pharmacokinetic consequences and brain barrier repulsion are getting onto this direction. Objective: Quetiapine fumarate, an analogous to above and an antischizophrenic agent, is tested for its diffusion property with and without lipophilic carrier through sheep nasal membrane. Being a BCS class II' and high permeable candidate, it tends to crossover easily, so made up in a simple dispersion. Materials and methods: To improve its diffusion rate, it was embedded into liposomal dispersion, which has proven that it has advanced efficiency for diffusion. For this, both the formulations were checked and compared for their diffusion profile, as it is an essential property for bioavailability through nasal route. Comparison was made on the basis of % drug diffusion within 6 h, rate, mechanism, profile, and coefficient. Results: Liposomal dispersion has been proved superior with greater percentage diffusion of 32.61 ± 1.70 and very high permeability with a coefficient value of 4.1334 ± 0.7321 (Â 10 À 5 cm/s). Diffusion profile comparison bearing dissimilarity of 18 and similarity of 74 indicated that the diffusion profiles of liposomal dispersions and simple dispersion were similar but not identical. Conclusion: Liposomal diffusion supremacy was further sustained by in vivo, ciliotoxicity, and gamma scintigraphy studies.

Liposomal Formulations for Nose-to-Brain Delivery: Recent Advances and Future Perspectives

“…Liposomal formulation of quetiapine fumarate, a schizophrenia drug, for the intranasal administration, was studied in a mice model [79]. The brain distribution of liposomes was first determined by gamma scintigraphy of 99m Tc and liposome-entrapped 99m Tc exhibited higher brain accumulation when compared to free 99m Tc dispersion.…”

“…Most works listed in Table 2 demonstrated the increased C max, prolonged drug distribution in the brain and longer duration of therapeutic effects by liposomal encapsulation [72,74,75,76,77,79]. Liposomes appear to help in overcoming the solubility limitations of lipophilic drugs and function as an intranasal drug depot slowly releasing these drugs.…”

“…However, differences in experimental details among the listed studies should still be mentioned. For example, studies were done in mice [76,79] or in rats [74,75,77,78]. Anatomical differences among species may affect the nasal blood flow, enzymatic activity, mucociliary clearance, and intranasal pH [51], thereby affecting nasal drug adsorption.…”

“…Anatomical differences among species may affect the nasal blood flow, enzymatic activity, mucociliary clearance, and intranasal pH [51], thereby affecting nasal drug adsorption. Administration positions were different: supine [79], prone [78], or not described [74,75,76,77]. Lowered brain C max by liposomal encapsulation of olanzapine shown by Salama [78] in opposite to increases in most studies [74,76,77,79] may be at least partly associated with the opposite administration position taken in Salama’s work.…”

“…Administration positions were different: supine [79], prone [78], or not described [74,75,76,77]. Lowered brain C max by liposomal encapsulation of olanzapine shown by Salama [78] in opposite to increases in most studies [74,76,77,79] may be at least partly associated with the opposite administration position taken in Salama’s work. The application of olfactory delivery-specialized device using liposome aerosol was attempted in one study [75], and it might result in much preferential drug accumulation in the olfactory region as compared to other works, in which drugs were applied without a specialized device.…”