Development and Characterization of Oral Raft Forming In Situ Gelling System of Neratinib Anticancer Drug Using 32 Factorial Design

Abstract

Neratinib (NTB) is an irreversible inhibitor of pan-human epidermal growth factor receptor (HER-2) tyrosine kinase and is used in the treatment of breast cancer. It is a poorly aqueous soluble drug and exhibits extremely low oral bioavailability at higher pH, leading to a diminishing of the therapeutic effects in the GIT. The main objective of the research was to formulate an oral raft-forming in situ gelling system of NTB to improve gastric retention and drug release in a controlled manner and remain floating in the stomach for a prolonged time. In this study, NTB solubility was enhanced by polyethylene glycol (PEG)-based solid dispersions (SDs), and an in situ gelling system was developed and optimized by a two-factor at three-level (32) factorial design. It was analyzed to study the impact of two independent variables viz sodium alginate [A] and HPMC K4M [B] on the responses, such as floating lag time, percentage (%) water uptake at 2 h, and % drug release at 6 h and 12 h. Among various SDs prepared using PEG 6000, formulation 1:3 showed the highest drug solubility. FT-IR spectra revealed no interactions between the drug and the polymer. The percentage of drug content in NTB SDs ranged from 96.22 ± 1.67% to 97.70 ± 1.89%. The developed in situ gel formulations exhibited a pH value of approximately 7. An in vitro gelation study of the in situ gel formulation showed immediate gelation and was retained for a longer period. From the obtained results of 32 factorial designs, it was observed that all the selected factors had a significant effect on the chosen response, supporting the precision of design employed for optimization. Thus, the developed oral raft-forming in situ gelling system of NTB can be a promising and alternate approach to enhance retention in the stomach and to attain sustained release of drug by floating, thereby augmenting the therapeutic efficacy of NTB.

Design and evaluation of in situ gel eye drops containing nanoparticles of Gemifloxacin Mesylate

“…Thermal DSC analyzer (Shimadzu, Singapore DSC − 60) was used to obtain DSC thermograms of pure drug Gemifloxacin Mesylate and Physical mixture of Gemifloxacin Mesylate, chitosan and Poloxamer 407. The sample was precisely weighed in an aluminum pan, then crimped with an aluminum cover and heated at a rate of 10 °C per minute from 30.0 °C to 300.0 °C (Hani et al., 2022 ).…”

“…Final batch was optimized using 3 2 Factorial Design with 2-factors, 3-levels and 9 runs by Design-Expert® software (Rahamathulla et al., 2021a ; Hani et al., 2022 ). In this study, Polymer (Chitosan) concentration (X1), Stirring speed (X2) were chosen as the independent variables.…”

Dual targeting multiwalled carbon nanotubes for improved neratinib delivery in breast cancer

“…38 The spectra of NT exhibited distinct absorption peaks at 3427 cm −1 (for N-H stretching vibrations); 3034 cm −1 (for C-H stretching vibrations); 2204 cm −1 (for C^N stretching vibrations); 1622 cm −1 (for C]O stretching vibrations). 39 The spectra of Bio-Chi showed distinct peaks at 3360; 3308 and 2928 cm −1 corresponding to the stretching vibration of O-H and N-H, and C-H, respectively. The peak at 1641 cm −1 indicates the bending amide bond formed between biotin and chitosan, suggested the possibility of a strong interaction between Bio and Chi.…”

Design and development of gastro-retentive gel forming system comprising curcumin loaded Nanostructured lipid carrier for stomach specific delivery

“…W1 denoted as initial weight of the gel. The gel was transferred to 10 ml of distilled water, and after a 30-minute interval, the weight of the gel was re-weighted, following the decanting of excess water, noted as W2 [10].…”

“…The formulation achieves a low bulk density through the release of CO2, enabling it to float on gastric fluids. This effect is brought about by a gelling agent, such as sodium alginate and alkaline bicarbonate, which induces CO2 generation, contributing to the formulation's buoyancy on gastric fluid [10]. The gels formed persist in the stomach for an extended duration.…”