Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.

High percentage of diabetic people are diagnosed as type 2 who require daily dosing of an antidiabetic drug such as Linagliptin (Lina) to manage their blood glucose levels. This study aimed to develop injectable Lina-loaded biodegradable poly (lactic-co-glycolic acid) (PLGA) in-situ implants (ISIs) to deliver a desired burst effect of Lina followed by a sustained release over several days for controlling the blood glucose levels over prolonged time periods. The morphological, pharmacokinetic, and pharmacodynamic assessments of the Lina-loaded ISIs were performed. Scanning electron microscopy (SEM) study revealed the rapid exchange between the water miscible solvent (N-methyl-2-pyrrolidone; NMP) and water during the ISI preparation, hence enhancing the initial burst Lina release. While, triacetin of lower water affinity could lead to formation of more compact and dense ISI structure with slower drug release. By comparing various ISI formulations containing different solvents and different PLGA concentrations, the ISI containing 40 % PLGA and triacetin was selected for its sustained release of Lina (93.06 ± 1.50 %) after 21 days. The pharmacokinetic results showed prolonged half life (t_1/2) and higher area under the curve (AUC) values of the selected Lina-loaded ISI when compared to those of oral Lina preparation. The single Lina-ISI injection produced a hypoglycemic control in the diabetic rats very similar to the daily oral administration of Lina after 7 and 14 days. In conclusion, PLGA-based ISIs confirmed their suitability for prolonging Lina release in patients receiving long-term antidiabetic therapy, thereby achieving more enhanced patient compliance and reduced dosing frequency.

Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX sublingual in situ gels were developed and assessed for their pH, gelling capacity, viscosity, mucoadhesion and in vitro drug release. The optimized gelling system demonstrated enhanced mucoadhesion, superior gelling capacity, reasonable pH and optimal rheological profile. In vivo, compared to the oral solution, the optimal sublingual gel resulted in a significant higher rate and extent of bioavailability. Although the in situ gel had comparable plasma levels to those observed following intravenous administration, significant amelioration of the systemic adverse reactions were attained. As demonstrated by the hot plate method, a sustained duration of analgesia in rats was observed after sublingual administration of DEX gel compared to the intravenously administered DEX solution. Furthermore, no changes in systolic blood pressure and heart rate were recorded in rats and rabbits, respectively, after sublingual administration of DEX. Sublingual administration of DEX in situ gel provides a promising approach for analgesia and sedation, while circumventing the reported adverse reactions associated with intravenous administration of DEX.

Purpose: Pregabalin (LYRICA ^® ) is a centrally acting neuromodulating agent for the management of neuropathic pain and fibromyalgia. Owing to its short half-life, LYRICA ^® controlled release (CR) tablets have been approved to be administrated once daily. However, the tablets are prepared by a multi-step process using a combination of release-controlling, wetting, pore-forming, and gelling agents. Hence, there is a need to develop a simple cost-effective environment-friendly methodology for the manufacturing of pregabalin extended release (ER) tablets. Methods: Quality by design (QbD) was applied for simple manufacturing of pregabalin extended release tablets with comparable efficacy to the reference product LYRICA ^® CR (82.5 mg) utilizing hydrophilic and lipid components and hot-melt granulation. The design of experiment (DoE) based on Taguchi model was utilized to investigate the effect of combination of various hydrophilic and lipophilic matrices, fillers and compression forces on the release of pregabalin ER tablets. Pre-compression blends were evaluated for micrometrics while tablets were evaluated for drug content, average weight, hardness, friability, thickness, dissolution and release kinetics. A pharmacokinetics study was performed to evaluate the pharmacokinetics profile of the optimized formulation as compared to the reference marketed product. Results: Results, analyzed using Minitab software ^® 18, determined significant and non-significant variables. The lipophilic meltable binder displayed significant effects on the pre-compression blend characters, yet not able to attain an extended release profile for pregabalin. Combination of hydrophilic and lipophilic matrices efficiently developed pregabalin tablets of extended-release pattern. The optimized formulation (composed of 80 mg of stearic acid, 100 mg of Methocel K15M and lactose with compression value of 10 KN) showed a comparable pharmacokinetics profile to the reference drug in terms of AUC (4.12 and 4.78 µg.h/mL, respectively) and C _max (0.31 and 0.36 µg/mL, respectively) using a pilot-scale bioequivalence study in albino rabbits. Conclusion: QbD and DoE can be effectively applied for the design and development of a timesaving and eco-friendly methodology for the preparation of pregabalin ER tablets as an alternative to the marketed product.