Design, development, and technical considerations for dry powder inhaler devices.

The dry powder inhaler (DPI) stands out as a highly patient-friendly and effective pulmonary formulation, surpassing traditional and other pulmonary dosage forms in certain disease conditions. The development of DPI products, however, presents more complexities than that of other dosage forms, particularly in device design and the integration of the drug formulation. This review focuses on the capabilities of DPI devices in pulmonary drug delivery, with a special emphasis on device design and formulation development. It also discusses into the principles of deep lung particle deposition and device engineering, and provides a current overview of the market for DPI devices. Furthermore, the review highlights the use of computational fluid dynamics (CFD) in DPI product design and discusses the regulatory environment surrounding these devices.

Safe Subunit Green Vaccines Confer Robust Immunity and Protection against Mucosal Brucella Infection in Mice.

Brucellosis is a zoonotic disease that causes significant negative impacts on the animal industry and affects over half a million people worldwide every year. The limited safety and efficacy of current animal brucellosis vaccines, combined with the lack of a licensed human brucellosis vaccine, have led researchers to search for new vaccine strategies to combat the disease. To this end, the present research aimed to evaluate the safety and efficacy of a green vaccine candidate that combines Brucella abortus S19 smooth lipopolysaccharide (sLPS) with Quillaja saponin (QS) or QS-Xyloglucan mix (QS-X) against mucosal brucellosis in BALB/C mice. The results of the study indicate that administering two doses of either sLPS-QS or sLPS-QS-X was safe for the animals, triggered a robust immune response, and enhanced protection following intranasal challenge with S19. Specifically, the vaccine combinations led to the secretion of IgA and IgG1 in the BALF of the immunized mice. We also found a mixed IgG1/IgG2a systemic response indicating evidence of both Th1 and Th2 activation, with a predominance of the IgG1 over the IgG2a. These candidates resulted in significant reductions in the bioburden of lung, liver, and spleen tissue compared to the PBS control group. The sLPS-QS vaccination had conferred the greatest protection, with a 130-fold reduction in Brucella burdens in lung and a 55.74-fold reduction in the spleen compared to PBS controls. Vaccination with sLPS-QS-X resulted in the highest reduction in splenic Brucella loads, with a 364.6-fold decrease in bacterial titer compared to non-vaccinated animals. The study suggests that the tested vaccine candidates are safe and effective in increasing the animals' ability to respond to brucellosis via mucosal challenge. It also supports the use of the S19 challenge strain as a safe and cost-effective method for testing Brucella vaccine candidates under BSL-2 containment conditions.

Xyloglucan based mucosal nanovaccine for immunological protection against brucellosis developed by supercritical fluid technology.

Vaccines delivered via the mucosal route have logistic benefits over parenteral or intramuscular vaccines as they offer patient compliance. This study presents the first intranasal, controlled release, subunit nanovaccine comprising mucoadhesive tamarind seed polymer (xyloglucan) based nanoparticles produced using an efficient, environmentally compatible, and industrially scalable technique: rapid expansion of supercritical solution. The nanovaccine formulation aimed against brucellosis comprised xyloglucan nanoparticles loaded separately with antigenic acellular lipopolysaccharides from B. abortus (S19) and the immunoadjuvant quillaja saponin. The nanovaccine elicited prolonged humoral and cell-mediated immunity in female Balb/c mice. Nasal vaccination with the nanovaccine resulted in higher levels of mucosal IgA and IgG than with an aqueous solution of soluble lipopolysaccharides and quillaja saponin. Systemic immunity triggered by the nanovaccine was evidenced by higher IgG levels in sera post priming and boosting. The nanovaccine induced a mixed Th1/Th2 type of immunity with higher IgG2a levels and thus a polarized Th1 response. The results suggest that the nanovaccine administered by homologous nasal route can prime the immune system via the mucosal and systemic pathways and is a good candidate for vaccine delivery.

Cefoperazone sodium liposomal formulation to mitigate P. aeruginosa biofilm in Cystic fibrosis infection: A QbD approach.

Cystic fibrosis (CF), an atypical genetic disorder, develops due to mutations in cystic fibrosis transmembrane conductance regulator gene, which consequently leads to infection and inflammation. CF infections are commonly characterized by the presence of an extracellular polymeric substance (EPS) matrix or the 'biofilm', which presents an entry barrier for the antibiotics. The current research work focuses on systematic Quality by Design based development of cefoperazone sodium loaded liposome formulation. DPPC and cholesterol containing liposomes were formulated by using 'thin film hydration' method. The freeze drying and further characterization of optimized formulation was carried out for particle size distribution, % entrapment efficiency, FTIR, DSC and pXRD. The IC50 value of the formulation (0.42 µg/ml) was found to be half of that of the drug (0.92 µg/ml). The formulation showed 50% biofilm inhibition and eradication at ~1 µg/ml. The cell surface hydrophobicity was reduced to ~50% at MIC value of the formulation while it was 78% for the control. The EPS component of P. aeruginosa biofilm reduced to 17% after treatment with 0.42 µg/ml formulation. The effect of formulation on biofilm was further confirmed by SEM analysis which revealed that the biofilm was disintegrated on treatment with 0.42 µg/ml of formulation.

Performance Parameters and Characterizations of Nanocrystals: A Brief Review.

Poor bioavailability of drugs associated with their poor solubility limits the clinical effectiveness of almost 40% of the newly discovered drug moieties. Low solubility, coupled with a high log p value, high melting point and high dose necessitates exploration of alternative formulation strategies for such drugs. One such novel approach is formulation of the drugs as "Nanocrystals". Nanocrystals are primarily comprised of drug and surfactants/stabilizers and are manufactured by "top-down" or "bottom-up" methods. Nanocrystals aid the clinical efficacy of drugs by various means such as enhancement of bioavailability, lowering of dose requirement, and facilitating sustained release of the drug. This effect is dependent on the various characteristics of nanocrystals (particle size, saturation solubility, dissolution velocity), which have an impact on the improved performance of the nanocrystals. Various sophisticated techniques have been developed to evaluate these characteristics. This article describes in detail the various characterization techniques along with a brief review of the significance of the various parameters on the performance of nanocrystals.

Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride.

Lercanidipine hydrochloride is a calcium channel blocker used in the treatment of hypertension. It is a poor water soluble drug with absolute bioavailability of 10%. The aim of this study was to design lercanidipine hydrochloride-loaded nanostructured lipid carriers to investigate whether the bioavailability of the same can be improved by oral delivery. Lercanidipine hydrochloride nanostructured lipid carriers were prepared by the method of solvent evaporation at a high temperature and solidification by freeze drying. The nanostructured lipid carriers were evaluated for particle size analysis, zeta potential, entrapment efficiency, in vitro drug diffusion, ex vivo permeation studies and pharmacodynamic study. The resultant nanostructured lipid carriers had a mean size of 214.97 nm and a zeta potential of -31.6 ± 1.5 mV. More than 70% lercanidipine hydrochloride was entrapped in the NLCs. The SEM studies indicated the formation of type 2 nanostructured lipid carriers. The in vitro release studies demonstrated 19.36% release in acidic buffer pH 1.2 indicating that the drug entrapped in the nanostructured lipid carriers remains entrapped at acidic pH. The ex vivo studies indicated that the drug release was enhanced from 10% to 60.54% at blood pH in 24h. The in vivo pharmacodynamic study showed that NLCs released lercanidipine hydrochloride in a controlled manner for a prolonged period of time as compared to plain drug. These results clearly indicate that nanostructured lipid carriers are a potential controlled release formulation for lercanidipine hydrochloride and may be a promising drug delivery system for the treatment of hypertension.