Journal of Pharmaceutical Innovation最新文献

The affordability and accessibility of generic medications drive their dominance in the U.S. market. Competitive Generic Therapy (CGT) exclusivity promotes efficient development, expedited market entry, and swift reviews for drugs with inadequate competition. This study examines CGT exclusivity approvals from January 2019 to October 2024, focusing on therapeutic areas with limited competition and the impact on patient access. Of 353 applications reviewed, 126 exclusivities granted from 2019 to 2023 were analysed. The average time to market was assessed, excluding 2024 due to unavailable marketing dates. One of the key findings of this study highlights the disparity in marketing timelines between generics approved for life-threatening versus non-serious conditions. While CGT-designated drugs for life-threatening conditions reach the market faster (21.53 days on average), those for non-serious conditions experience longer delays (29.56 days on average). External factors like market demand and competition risk greatly impact CGT exclusivity, driving manufacturers to prioritize critical therapies to trigger exclusivity while ensuring generic accessibility in the U.S. market. By analysing the landscape of CGT exclusivity approvals, this study emphasizes how these regulatory measures tackle areas of inadequate competition, thereby enabling quicker patient access to vital therapies. The research identifies how CGT exclusivity helps in rapid access to generic drugs in the U.S. market. In conclusion, this study underscores the effectiveness of CGT exclusivity in reducing time-to-market for generics, thereby improving accessibility and addressing gaps in competition. These insights emphasize the importance of regulatory measures like CGT exclusivity in promoting accessibility while addressing the broader challenges of generic competition.

Purpose

Torasemide is a diuretic used to treat heart failure, edema, liver and kidney diseases, and hypertension.However, its poor solubility and short half-life (3.5 h) necessitate frequent dosing. To overcome these limitations, this study aims to develop a gastroretentive in situ floating gel for Torasemide, utilizing raft-forming and in situ gel-forming systems to enhance gastric retention and sustain drug release for precise gastrointestinal delivery.

Methods

A Torasemide in situ gastric floating gel for sustained drug release was formulated to improve solubility through 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) complexation and optimised using central composite design (CCD). Sodium Alginate (X1) and Gellan Gum (X2) were varied at five levels to evaluate the effects on viscosity (Y1) and floating lag time (Y2) as response variables. Design of Experiment (DoE) software guided the preparation of 13 formulations with varying concentrations of these independent variables.

Results

The optimised batch demonstrated a viscosity of 182.26 cps and a floating lag time of 81.36 s, achieving notably superior performance with 89.51% cumulative drug release over 12 h compared to 52.85% for pure Torasemide in the gelling base. The release profile aligned best with the Hixon-Crowell model. X-ray imaging verified 12-h gastric retention in the in vivo rabbit model, and stability studies confirmed that the formulation remained stable for over 3 months under accelerated conditions (40 ± 2 °C/75 ± 5% RH).

Conclusion

This innovative formulation holds promise as a therapeutic advancement. By forming the complex with 2-hydroxypropyl-β-cyclodextrin, the formulation significantly enhances Torasemide's solubility and bioavailability, enabling sustained drug release and thereby improving therapeutic efficacy in managing hypertension and related conditions.

Background

Omega-3 fatty acids (O3FA) and statins effectively reducing the levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), respectively, and are actively used in clinical practice worldwide for the treatment of hyperlipidemia. Combinations of O3FA and statins have been found effective in managing complex dyslipidemia cases and achieving synergistic therapeutic effects while improving patient compliance.

Purpose

This study was conducted to examine the current status of the development of combinations of O3FA and statins, which have recently been garnering attention, and to consider future approaches to developing additional formulations.

Methods

By reviewing published literature and market reports, we summarize the development status of O3FA and statin combinations. We also identified a scope for improvement in such formulations and propose new formulation development approaches.

Results

Co-administration of direct physical combinations of O3FA and statins is generally considered safe and free of drug interactions, but inherent challenges to drug stability exist. In particular, O3FA oxidation is highly possible, necessitating a spatially separated combination technology without direct contact with statins. An attempt to encapsulate O3FA within soft capsules and statin drugs as powders, granules, or tablets in a hollow capsule was proposed as a new approach that can solve both the stability issues due to potential interactions between ingredients and the content change issues due to ingredient loss during mechanical transport. In addition, a novel combination formulation with fibrate or ezetimibe was proposed to improve TG, cholesterol, and LDL-C levels while maximizing compliance in patients taking multiple medications.

Conclusion

Attempts to formulate combinations of anti-hyperlipidemic drugs are becoming popular in the management of complex dyslipidemia cases. In this context, this study presents important pharmaceutical perspectives on combining O3FA and statins. The findings presented herein provide useful insights into developing additional improved oral formulations in the future.

N-acetyl D-glucosamine (NAG) holds clinical significance in treating hyperpigmentation through its ability to inhibit melanin production, support skin barrier functions, and its favorable treatment profile that makes it suitable for various skin types. This study explores the characterisation of NAG and soya lecithin using Fourier Transform Infrared (FT-IR) spectrophotometry and evaluates ethosomal formulations for drug delivery applications. The zeta potential, pH, extrudability, spreadability, viscosity, and in vitro drug release of many ethosomal formulations were evaluated. An in vivo investigation evaluated hyperpigmentation in rats, and stability tests were conducted at 25 °C and 4 °C. The compatibility of both compounds was confirmed by FTIR, which also showed the presence of distinctive peaks. The diameters of particles varied from 649 to 6463 nm, and their zeta potentials fell between − 8.97 and − 18.63 mV. The range of drug entrapment efficiency was considerable, from 97.23 to 99.43%. Over 45 days, stability studies showed few changes. The pH, extrudability, spreadability, and viscosity of ethosomal gels ranged from 5.89 to 6.38, 45.17 to 63.93 gm/cm², and 6.66 to 10 cm, respectively. Zero-order and Korsmeyer models dominated in vitro drug release, which varied from 8.206 to 25.81%. Significant inflammatory alterations consistent with persistent dermatitis were revealed by histopathological examinations in the in vivo investigation. The findings show potential for treating skin problems by showing that ethosomal formulations of NAG are stable and effective for medication delivery.

Purpose

The objective of the current study is synthesis and optimization of Nasal Insitu Gel loaded with Risperidone (RIS) and Quercetin (QUE) Solid Lipid Nanoparticles (SLN) by Design Expert and Quality by Design (QbD)Approach.

Method

QTTP (Quality target product profile), critical process parameters (CPP), critical quality attributes (CQAs) were identified. Preliminary screening of factors which affect CPP and CQAs was carried out using Placket Burman design. SLN were prepared by solvent diffusion method. Optimization of SLN was carried by 2² (RIS) and 2³ (QUE) factorial designs. Temperature, Type of co-surfactant, Concentration of surfactant (%) were identified as independent factors and responses were recorded against Particle size, % Entrapment Efficiency. Characterization of prepared SLN were done by analysis of particle size, PDI, Zeta Potential, FTIR, Entrapment Efficiency, TEM etc., synthesized SLN were incorporated into Insitu gel which was evaluated for gelation temperature, viscosity, in-vitro drug diffusion etc.

Results

RIS SLN and QUE SLN were successfully synthesized. Particle size was found 157.4 ± 2 nm 153 ± 3 nm. Respectively. PDI was observed 0.261 for RIS SLN and 0.240 and QUE SLN. % EE were obtained 91.73 ± 2.6%, 91.73 ± 2.6% respectively indicated successful drug encapsulation. TEM study supported spherical nature. DSC and FTIR study showed successful incorporation of drugs into SLN. SLN were successfully incorporated into 18% concentration of poloxamer for formation of nasal insitu gel. In-vitro diffusion study revealed sustained and controlled drug release.

Conclusion

The study successfully developed and optimized SLNs loaded with RIS and QUE SLN for nasal administration using the QbD approach. The combination of SLNs and insitu gel provided a stable and effective nasal delivery system. The developed SLNs and insitu gel formulation are promising for nasal administration, offering a viable alternative to oral delivery by effectively bypassing first-pass metabolism and improving drug availability.

Purpose

Alpha lipoic acid (ALA) is a natural compound that has recently gained attention for its anti-inflammatory potential. ALA has a low bioavailability and in vitro stability, making its clinical use a challenge. Lipid–polymer hybrid nanoparticles (LPHNPs), a newly discovered core-shell nanostructures, are derived from liposomes and polymeric nanoparticles, and they were commonly used to improve in vivo efficiency and stability of active substances.

Methods

The current study aimed to prepare ALA-loaded LPHNPs via the design of experiments (DoE) approach to improve oral bioavailability and in vitro stability of ALA. The Plackett-Burman design was used to select independent variables by evaluating the effects of drug amount, stirring rate, polymer amount, lipid/polymer ratio, water/organic solvent (W/Os) ratio, and polyvinyl alcohol (PVA) concentration on formulation properties. Afterward, statistically significant formulation parameters were optimized using the Box-Behnken design (BBD). Finally, the in vitro properties were evaluated, and the in vivo anti-inflammatory effect of the optimized formulation was tested using formalin-induced paw edema in mice.

Results

The main factors affecting the mean particle size (mPS), polydispersity index (PdI), and ζ potential (ZP) values of ALA-loaded LPHNPs were the stirring rate, W/Os ratio, and PVA concentration; however, the independent variables had no significant effect on encapsulation efficiency (EE). Furthermore, optimized ALA-loaded LPHNPs also significantly reduced paw edema thickness and volume with a prolonged duration of action compared to ALA solution during 6 h after formalin administration.

Conclusion

The optimized ALA-loaded LPHNPs with core-shell structure had sustained control release up to day 17 and exhibited superior colloidal and chemical stability under various in vitro conditions and prolonged and robust in vivo anti-inflammatory effect.

Graphical Abstract

Purpose

The objective is to study the influence of surfactant chain lengths on the solubilization capacity and release pattern from the Rosuvastatin calcium-loaded microemulsion.

Methods

In the study, rosuvastatin calcium was incorporated into oil-in-water microemulsion formulations using surfactants of varying chain lengths. The developed formulations were then characterized for physicochemical properties, along with stability, release profile and in vitro intestinal permeability. The cytotoxicity assay was performed to assess the safety of microemulsion formulation.

Results

The stability of microemulsion formulation increases with the increase in carbon chain as indicated with smaller globule size, excellent dispersibility, and reduced dynamic surface tension. Furthermore, the stable rosuvastatin calcium-loaded microemulsion showed relatively higher transmittance value which was observed to be decreased with their dilution over time. The release study showed that the formulations with longer chain length surfactants exhibited higher rate of drug release in both SGF and SIF. The release kinetics of the developed formulation follow zero order equation and release mechanism was identified as supercase-II transport type diffusion. Additionally, the selected microemulsion system did not show any signs of cytotoxic potential on HCT-116 cells.

Conclusions

It can be concluded that the use of surfactant with longer chain length showed improvement in the transport of the drug through the lipid-rich membrane of intestine. The stable microemulsion allows regulation of epithelial cells and facilitating the paracellular transport of the drug.

Graphical Abstract

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by inflammation due to autoantibodies against nuclear antigens. Current treatments suffer from poor bioavailability, low specificity, and significant side effects. Nanoparticle (NP)-based drug delivery systems offer promising alternatives through enhancing solubility, stability, bioavailability, controlled release and targeted delivery of drugs. Recent studies have demonstrated that NPs with various structures provide a novel approach for treating SLE, potentially reducing side effects while improving efficacy of therapeutic agents. This review aims to present the current status of SLE therapy, along with the potential advantages and challenges of using NPs in diagnosis and treatment of SLE.

Purpose

In the present study, a novel pongamia oil combination-based chloramphenicol (CPL)-coloaded curcumin (CUR) nanoemulsion (NE)-fortified chitosan hydrogel was formulated for effective wound healing.

Methods

The nanoemulsion was optimized by a central composite design. The factors that exhibited a significant (ANOVA) effect on the responses were studied. FT-IR and DSC studies indicated the compatibility of the drugs with excipients. The selected independent variables were Pongamia oil (PO): Tween 80: propylene glycol (PG), stirring time (ST) and sonication time, and the dependent variables selected were globule size and PDI.

Results

The globule size of the formulations F15a & F15b was found to be 280.23 ± 0.21 and 276.45 ± 0.29 nm, with PDIs of 0.390 ± 0.02 and 0.593 ± 0.02 and zeta potentials of -65.43 ± 0.39 and -70.73 ± 0.63 mV, which confirmed the uniform globule size distribution and stability of the formulations. Compared with the plain drugs, formulations F15a and F15b presented a greater zone of inhibition against Staphylococcus aureus (38 & 35 mm) and E. coli (32&29 mm). TEM analysis revealed a nearly spherical shape of the globules that was free from coalescence. The invitro drug release data indicated sustained drug release for up to 72 h. The exvivo drug release rates of F15a and F15b were 92.4% and 95%, respectively, for CPL and 87.6% and 94%, respectively, for CUR at 24th h. Contour plots were used to select the desired batch range. The stability studies indicated that the formulations remained stable at 40 ± 2 °C and an RH of 75 ± 5%. Compared with the control (70.00 ± 0.18%) and standard (92.04 ± 0.84%) groups, the optimized NE-CPL-CUR hydrogel F15a & F15b-treated groups exhibited greater wound contraction (94.44 ± 0.56 & 99.08 ± 0.18%) at the end of 21 days. Histopathological studies revealed better and improved reepithelization and epidermal and dermal regeneration.

Conclusion

The results of the present study demonstrated that the developed NE-CPL-CUR (0.5:1; CPL and CUR) chitosan-based hydrogel provided better wound healing because of the synergistic combination and presence of Pongamia oil in the nanoemulsion.

Objectives

The tablet of multi-unit pellet system (TMUPS) tends to enable diversified therapeutic outcomes, due to the characteristic of containing pellets with different release behaviors. In the development of TMUPS formulations, it is essential to uniformly blend the pellets to ensure that the drug release profile of the formulation meets expectations.

Methods

In order to achieve the characterization of the blending status of sinomenine hydrochloride pellets and determine the blending endpoint, a method based on the machine vision (MV) technique combined with the independent circle (IC) image analysis algorithm was proposed. Fifteen experimental batches of the blending process with varying conditions were designed for the research. The images of pellets distribution at six different layers were captured using a MV photography platform, and the spatial distribution of the pellets during the blending process was digitally characterized using the IC algorithm.

Results

Compared to the traditional counting method, the utilization of the MV technique allowed for the accurate and timely determination of the blending endpoints of all batches and enabled the monitoring of changes in the blending status to detect when the demixing phenomenon occurred, based on the proportions, total number, and area occupied by the two types of pellets.

Conclusions

The MV method established in this paper may serve as a potential strategy for the monitoring of the relatively complex blending process involving multiple types of pellets with similar properties.