Pharmaceutical Development and Technology最新文献

Drug abuse has become a global health problem over the past few years. Opioid abuse increased with an increase in the prescription of opioids for pain management. Many other classes of drugs are also abused and misused like anti-depressants, stimulants, hallucinogens, anti-psychotic, and anticholinergic drugs. One of the major reasons is that patients falsely diagnosed with depression, anxiety, and severe pain are prescribed these drugs, which are likely to be addictive. Abuse-deterrent formulations are one means to control drug abuse and overdose of prescription opioids. In this review, we explained how abuse-deterrent technology works, key ingredients used in abuse-deterrent formulations, a brief about marketed opioid drug products with abuse-deterrent properties, and the stand of regulatory agencies in the approval process of opioid drug products. In the end, it summarized that pharmaceutical industries and the FDA put their efforts into reducing drug abuse by encouraging the development of ADFs. Most available drug product having abuse-deterrent features contains Polyethylene oxide, which degrades at high temperatures. It requires the attention of the researcher to find an alternate ingredient or process to overcome said problem. From a regulatory point of view, only a few regulatory agencies have published their guidance on ADFs. It is important to convey other regulatory organizations' perspectives on ADFs as well.

Objective: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen.

Methods: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit^®L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH.

Results: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated C_max (18.35 µg/ml compared to 11.1 µg/ml).

Conclusion: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release.

The increasing prominence of biologics in the pharmaceutical market requires more advanced delivery systems to deliver these delicate and complex drug molecules for better therapeutic outcomes. Fibre technology has emerged as a promising approach for creating controlled and targeted drug delivery systems. Fibre-based drug delivery systems offer unprecedented opportunities for improving drug administration, fine-tuning release profiles, and advancing the realm of personalized medicine. These applications range from localized delivery at specific tissue sites to systemic drug administration while safeguarding the stability and integrity of delicate therapeutic compounds. Notwithstanding the promise of fibre-based drug delivery, several challenges such as non-scalability impede cost-effectiveness in the mass production of fibre systems. Biocompatibility and toxicity concerns must also be addressed. Furthermore, issues relating to stability, in-vitro in-vivo correlations, degradation rates, and by-product safety present additional hurdles. Pharmacoinformatics shows the impact of technologies in pharmaceutical processes. Emerging technologies such as Artificial Intelligence (AI) are a transformative force, progressively being applied to enhance various facets of pharmacy, medication development, and clinical healthcare support. However, there is a dearth of studies about the integration of AI in facilitating the translation of predominantly lab-scale pharmaceutical technologies into real-world healthcare interventions. This article explores the application of AI in fibre technology, its potential, challenges, and practical applications within the pharmaceutical field. Through a comprehensive analysis, it presents how the immense capabilities of AI can be leveraged with existing fibre technologies to revolutionize drug delivery and shape the future of therapeutic interventions by enhancing scalability, material integrity, synthesis, and development.

Hesperidin (HSP) is a natural flavonoid glycoside with very low aqueous solubility and a slow dissolution rate, limiting its effectiveness. This study aims to address these issues by creating co-crystals of hesperidin with water-soluble small molecules (co-formers) such as L-arginine, glutathione, glycine, and nicotinamide. Using the solvent drop grinding method, we prepared three different molar ratios of hesperidin to co-formers (1:1, 1:3, and 1:5) and conducted in-vitro solubility and dissolution studies. The results demonstrated that the prepared co-crystals exhibited significantly enhanced solubility and dissolution rates compared to untreated hesperidin. Of particular note, the HSP co-crystals formula (HSP: L-arg 1:5) displayed approximately 4.5 times higher dissolution than pure hesperidin. Further analysis using FTIR, powder x-ray diffraction patterns, and DSC thermograms validated the formation of co-crystals between HSP and L-arginine. Additionally, co-crystallization with L-arginine improved the in vitro anti-inflammatory and antioxidant activities of hesperidin compared to the untreated drug. This study highlights the potential of using water-soluble small molecules (co-formers) through co-crystallization to enhance the solubility, dissolution, and biological activities of poorly water-soluble drugs. Furthermore, in vivo studies are crucial to validate these promising results.

The study aimed to fingerprint the physical manufacturing properties of five commonly used acid sources in effervescent systems for designing the formulation and process of such systems. The hygroscopicity, texture properties, rheological torque, compressibility, tabletability, etc., were investigated to inspect 'powder direct compression (DC)' and 'wet granulation and compression' properties of citric (CA), tartaric (TA), malic (MA), fumaric (FA), and adipic acid (AA). The DC ability was evaluated by the SeDeM expert system. The results indicated that all acid powders failed to meet flowability requirements for DC, and plastic deformation dominated during compression. Furthermore, CA exhibited strong hygroscopicity and punch sticking, while MA demonstrated the best tabletability. TA had a large wet granulation space and was relatively the most suitable for DC. AA was extremely hygroscopic, and its flowability improved significantly as particle size increased. Finally, FA displayed the lowest hygroscopicity and ejection force as well as great compressibility and wet granulation space, and did not exhibit punch sticking, while the granule fragments dissolved slowly during disintegration. Generally speaking, the formulation or granulation affected the tabletability, indicating that pairing with other acids or suitable fillers could potentially improve its disadvantages. These multidimensional assessments effectively reduce the pre-exploration and enhance the efficiency of the development of effervescent systems.

Thermoresponsive nanoparticles are exploited as drug-delivery vehicles that release their payload upon increment in temperature. We prepared and characterized thermoresponsive lipid-anchored folic acid engineered magnetic nanoparticles (LP-HP-FANPs) that combine receptor-based targeting and thermoresponsive sustained release of hesperidin (HP) in response to endogenous inflammation site temperature. The progressive surface engineering of NPs was validated by FTIR analysis. Our LP-HP-FANPs had a particle size of 100.5 ± 1.76 nm and a zeta potential of 14.6 ± 2.65 mV. The HP encapsulation effectiveness of LP-HP-FANPs is around 91 ± 0.78%. AFM scans indicated that our modified nanoparticles were spherical. LP-HP-FANPs exhibit increased drug release (85.8% at pH 4.0, 50.9% at pH 7.0) at 40 °C. Animal studies showed no toxicity from nanoparticles. Compared to conventional drugs and HP, LP-HP-FANPs effectively decreased paw edema, cytokine levels, and total cell recruitment in thioglycollate-induced peritonitis (p < 0.05). LP-HP-FANPs substantially decreased cytokines compared to HP, HP-FA-NPs, and the standard medication (p < 0.05, p < 0.01, and p < 0.001). These findings imply that the synthesized HP-loaded formulation (LP-HP-FANPs) may be a potential anti-inflammatory formulation for clinical development.