The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson’s disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 3² full factorial design using Design-Expert^® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X₁) and HPMC K4M (X₂) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X₁ and 0.2% of X₂ with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings.

Depression is a complex psychiatric disorder marked by persistent emotional disturbances such as sadness, hopelessness, and fatigue, frequently accompanied by psychosocial impairments. Current treatment approaches are hindered by limited efficacy, poor patient adherence, and the inability of many therapeutic agents to effectively penetrate the blood-brain barrier (BBB). The BBB, a selective and protective interface between the bloodstream and brain tissue, restricts drug delivery to the central nervous system (CNS), resulting in suboptimal concentrations of antidepressants at the target site and delayed therapeutic responses. This review explores the limitations of conventional drug delivery systems for depression and highlights the intranasal route as a promising non-invasive alternative for direct brain targeting. Intranasal delivery bypasses hepatic first-pass metabolism and systemic degradation, offering rapid drug absorption and CNS access through olfactory and trigeminal neural pathways. Among emerging strategies, nanotherapeutics have gained increasing attention due to their capacity to improve solubility, protect labile compounds, and provide sustained drug release. Nanoparticles can encapsulate both hydrophilic and lipophilic drugs, enhancing their pharmacokinetics and stability. When administered intranasally, these nanocarriers can directly reach the brain, potentially reducing dosage frequency and enhancing therapeutic outcomes, while minimizing systemic side effects. This review focuses on the latest advancements in intranasal nanotherapeutic formulations for depression, such as polymeric nanoparticles, nanoemulsions, solid lipid nanoparticles, and nanostructured lipid carriers. The synergistic integration of nanotechnology and targeted CNS delivery offers a transformative approach to overcome the challenges posed by the BBB and improve depression management. While preclinical findings are promising, further clinical studies are necessary to confirm safety, efficacy, and long-term outcomes. Overall, intranasal nanotherapeutics represent a compelling direction for the development of next-generation antidepressant therapies, aiming to achieve faster onset, improved adherence, and enhanced quality of life for patients suffering from depression.

The present research is focused on developing floating matrix tablets of mitiglinide to prolong its gastric residence time for better absorption. Gastroretentive tablets were prepared using a direct compression technique with hydroxypropyl methylcellulose K15M (HPMC K15M) and sodium alginate as matrix-forming polymers and sodium bicarbonate as the gas-forming agent. A 3² full factorial design was adopted to optimize the flotation and release profile of the drug. The concentration of HPMC K15M and sodium alginate were taken as the independent variables, and the floating lag time, time required for 50% drug release, and time required for 90% drug release were taken as dependent variables. The compatibility between drug and excipients was assessed by Fourier transform infrared (FTIR) spectroscopy. The prepared tablets were evaluated for different parameters such as hardness, friability, drug content, floating time, in vitro dissolution, and stability. Dissolution data were analyzed using various kinetic models to ascertain the mechanism of drug release. Finally, a radiographic study was conducted to estimate the retention time of the optimized floating matrix tablets of mitiglinide inside the body. The results revealed that all the physical properties of the developed formulations were within standard limits. The formulation M3, with the maximum amount of both independent variables, was considered to be the optimized formulation based on the desirability value. In addition, the optimized M3 formulation showed stability for over 6 months, as evidenced by insignificant changes in lag time, drug release pattern, and other physical properties. Furthermore, radiographic examination indicated that the tablets remained afloat in gastric fluid for up to 12 h in the rabbit’s stomach. In conclusion, the developed floating matrix tablet of mitiglinide could be regarded as a promising formulation that could release the drug in the stomach at a controlled rate and, hence, offer better management of type II diabetes.