Drug Development and Industrial Pharmacy最新文献

Objective: The Saudi market offers dosages of metformin that have varying release rates and can lead to different pharmacological reactions. Studying formulation bioequivalences helps patients choose the optimum medicine without affecting pharmacological responses.

Significance: This study affects patient care clinically, which can improve Saudi diabetes management by improving efficacy, safety, adherence, access, and cultural relevance.

Method: The bioequivalence and pharmacokinetic parameters were studied using the convolution method. Similarity factor f₁ and different factors f₂ of different types of metformin tablets were calculated. Furthermore, the pharmacokinetic parameters were estimated using the convolution method.

Results: At pH = 6.8 (phosphate buffer) and 50 rpm, 100% of metformin was released within 2 h. While, after two hours in HCl at pH = 1.1 followed by five hours in phosphate buffer at pH = 6.8, 100% of the medication was released after 7 h. The release kinetics showed zero-order kinetics with r² = 0.961 for Formit^® and 0.971 for Glucophage^®, while the release mechanism showed that it follows the Higuchi equation with r² = 0.974 for Formit^® and 0.971 for Glucophage^®, respectively, indicating that the mechanism of drug release was controlled by diffusion. The two brands were lyo-equivalent, with a similarity factor and difference factor equal to 59.36 and 7.26, respectively.

Conclusion: The convolution approach indicated that Glucophage^® and Formit^® have bioequivalent C_max of 601 and 592 ng/ml, respectively. The two products had the same projected T_max of 2.0 h and a modest AUC_∞ differential that did not violate the FDA's 80-125% limit.

Objectives: This study presents a sustainable extraction process for obtaining plant active substances (PAS) from the leaves of Salvia rosmarinus Spenn. (rosemary) and semi-solid microemulsions (SSME) at the same time. The extraction method uses a sustainable solvent system of surfactants, co-surfactants, and water, yielding high PAS miscibility.

Methods: The method was developed using pseudo-ternary phase diagrams, particle size determination and ultrasound-assisted extraction. Optimization was performed via response surface methodology, assessing antioxidant capacity, total phenols, terpenoids, and flavonoids for efficiency evaluation.

Results: Optimal extraction conditions, identified using response surface methodology, which produced SSME with high antioxidant capacity (0.04 to 0.150 mmol/ml) and significant polyphenolic content (0.055 to 0.219 mg of gallic acid/ml). Additionally, the resulting formulations showed a total terpenoid content of 0.04 to 0.150 mmol/ml and a total flavonoid content of 5.4 to 10.5 mg/ml mg quercetin equivalent/ml. The droplet size and polydispersity index values of the optimized extracts were evaluated, yielding mean droplet sizes below 250 nm, indicating the presence of microemulsions. By means of UPLC-ESI-MS/MS the primary PAS were identified, validating the effectiveness of the extraction process in isolating of bioactive compounds with therapeutic potential.

Conclusions: This eco-friendly method not only aligns with green chemistry principles but also supports the development of PAS-rich SSME as candidates for dermal therapies.

Purpose: Oridonin (ORI) is an ent-kaurene tetracyclic diterpenoid with anti-tumor activities in various tumor cell lines. However, its hydrophobicity and non-targeting have greatly limited the clinical application of ORI. In the present study, long-circulating liposomes loading ORI and targeting lung cancer cells were established to solve these problems.

Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene-glycol (DSPE-PEG), modified with a homing peptide with the sequence YSAYPDSVPMMSK (YSA), was employed to constitute the matrix of liposomes in combination with soybean lecithin and cholesterol. Meanwhile, the characterization, stability, in vitro release, and delivery in vitro and in vivo of the prepared liposomes were studied.

Results: The results revealed that the prepared ORI-loaded liposomes exhibited a regular sphere with particle size of 140.64 ± 12.94 nm. The prepared liposomes showed good stability at 5 °C and sustained release profile in PBS solution. YSA modification to the liposomes enabled increased uptake by human lung cancer A549 cells, thereby increasing cytotoxicity on A549 cells. The pharmacokinetics study showed a higher area under the concentration time curve (AUC), a longer mean residence time (MRT), a slower plasma clearance (CL) and a prolonged half life time (t1/2) for ORI-loaded liposomes. Of important, the prepared liposomes exhibited a concentrated distribution in tumor tissues after intravenous injection. Therefore, ORI-loaded liposomes significantly inhibited tumor growth in tumor xenograft nude mice inoculated with A549 cells.

Conclusion: In conclusion, the constructed ORI-loaded liposomes might be a novel and promising delivery system for ORI in the treatment of lung cancer.

Objective: To enhance the aqueous solubility and dissolution rate of cilnidipine (CLN), a BCS Class II antihypertensive drug with poor oral bioavailability (13%), by developing oral nanocrystals (NCs) using a scalable antisolvent precipitation and high-speed homogenization technique.

Significance: CLN's therapeutic potential is limited by its low solubility. This study addresses this challenge through nanocrystal formulation, offering a cost-effective and industrially viable strategy to improve bioavailability and dissolution performance.

Methods: CLN-NCs were prepared by antisolvent precipitation coupled with high-speed homogenization. Stabilizers (PVPk30, mannitol), drug concentrations, and flow rates were systematically optimized. The lead formulation (F19) was characterized for particle size, saturation solubility, and dissolution rate. Solid-state properties were evaluated using SEM, XRPD, DSC, and FTIR to confirm crystalline stability.

Results: The optimized NCs (F19) exhibited a nanosized particle diameter (19.1 ± 3.8 nm), a 3.3-fold increase in saturation solubility, and a 4.1-fold faster dissolution rate compared to raw CLN. XRPD and DSC confirmed retained crystallinity, while FTIR revealed no drug-stabilizer interactions. SEM showed uniform morphology with no aggregation.

Conclusions: CLN-NCs significantly improved in vitro solubility and dissolution, demonstrating a scalable preparation method suitable for industrial translation. This approach offers a promising pathway to enhance CLN's therapeutic efficacy in hypertension management.

Objective: This study aimed to compare the dissolution kinetics of sustained-release bolus tablets formulated with different pharmaceutical binders using two systems-the continuous-flow artificial saliva rig and the Ankom Daisy II incubator-to evaluate how the experimental setup influences the interpretation of release behavior and kinetic modeling.

Significance: A precise understanding of method-dependent variations is critical for designing reliable sustained-release veterinary formulations. By isolating the effect of the testing environment itself, this study provides a methodological perspective that enhances the predictive accuracy of in vitro systems and supports the development of cost-effective, sustainable approaches in ruminant drug delivery research.

Methods: Bolus tablets containing 1% or 2% binder (starch, polyvinylpyrrolidone-PVP, or gum acacia-GA) were tested using a continuous-flow artificial saliva system and the Daisy II incubator with real rumen liquor. Granule morphology, particle size, bulk density, and mechanical strength were characterized. Dissolution kinetics were analyzed through standard models, and the model fits were evaluated using R² and AIC parameters.

Results: The binder composition and test environment had a significant impact on the release profiles. Starch-based bolus tablets dissolved rapidly, PVP showed moderate release, and GA provided prolonged, steady release. The Daisy II incubator produced stronger model correlations, with the 2% GA formulation showing the best fit (R²=0.9909, AIC=-71.08). The higher binder concentrations improved granule compactness and hardness.

Conclusions: The binder type and concentration strongly influence dissolution kinetics, while the testing environment determines release predictability. Gum acacia at 2% concentration achieved the most controlled and stable release, and the Daisy II incubator most accurately simulated rumen conditions for predictive in vitro evaluation.

Objective: The research is aimed at fulfilling long-term and high-performance synergistic anticancer effects of 5-fluorouracil (Flu), opening up new horizons for drug-nutrient cocrystal formulation.

Methods: An integration strategy of cocrystallization and micellar preparation techniques is established. The former targets to play synergistic effects by introducing nutriment ferulic acid (FR), and meanwhile, enhances the interplay with polymers to promote efficient encapsulation, whereas the latter focuses on the modulation of release behavior. Based on this clue, cocrystal Flu-FR-H₂O with synergistic ability is loaded in carriers to prepare cocrystal nanomicelles. The cocrystal nanomicelles were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM), with the in vivo/vitro biopharmaceutical properties evaluated.

Results: The obtained nanomicelles exhibit preferable encapsulation efficiency, as supported by theoretical simulation calculations. This higher efficient entrapment has positive impacts on antitumor efficacy and pharmacokinetic behavior. Particularly, the cocrystal micelles can provide sustained-release ability, thus facilitating the lasting-efficacy.

Conclusion: This investigation exemplifies the availability of the integrated strategy in realizing transformation of Flu-nutraceutical cocrystal dosage form, therefore contributing to the technical support for synergistic antitumor pharmaceutical cocrystal formulations.

Objectives: Etodolac (ETD), an insoluble anti-inflammatory drug, undergoes first-pass metabolism, which limits its oral bioavailability. The current study presents the trials for improvement of drug solubility on one hand and formulation of different emulgel systems loaded with modified drug on the other hand.

Significance: The Prolonged oral administration of ETD results in serious gastrointestinal problems. Therefore, the improvement of its solubility and modifying an alternative route of administration will increase its bioavailability and lessen its adverse effects, providing an alternative safe delivery system for inflammatory signs treatment.

Methods: The current study focused on the formulation of different emulgel systems since medicated emulgels were constructed by loading the emulgels with either pure ETD or modified ETD adsorbate (ETD/Avicel, 1:2 ratio). Finally, the in vivo studies were accomplished by studying the anti-inflammatory activity of ETD emulgels using albino rats.

Results: All the prepared emulgels showed acceptable physical properties since sodium alginate emulgel showed superior drug release compared with other gelling agents. The drug release profile was affected significantly by both emulsifying and gelling agents' concentration. The release kinetics data showed that the main mechanism of drug release was the Higuchi diffusion model. concerning the in vivo results, the extreme edema inhibition was obtained upon using emulgel formulae containing modified ETD with penetration enhancer (5% PG + 5% oleic acid). The modified emulgels did not show any sign of irritation on rats' dorsal skin.

Conclusion: The obtained results highlighted the promising application of topical ETD emulgels as an alternative anti-inflammatory drug delivery system.

Introduction: Formulation research benefits from high-throughput excipient screening methods, considering the ever-growing excipient space. We investigate the use of 384-well plates as freeze-drying containers and for subsequent analyses, to screen the effect of excipients on the stability of proteins during freeze-drying.

Methods: For both the preparation and analysis methods of a range of β-galactosidase formulations, an 8-tip pipetting robot was used. Formulations were lyophilized in 384-well plates, which were also used for subsequent enzymatic activity assessment, serving as an indication of protein stability.

Results: Excipient screening revealed that threonine, histidine, arginine, sucrose, and trehalose enhance the recovery of the enzymatic activity of β-galactosidase compared to the protein freeze-dried in buffer without other excipients. Moreover, pullulan only showed a stabilizing effect when it was combined with low-molecular-weight excipients that by themselves were poor stabilizers, which was especially the case for serine and to some extent for valine.

Discussion: There were no significant differences in enzymatic activity when comparing the automated 384-well plate freeze-drying method with a common in-vial method, while offering the added sustainability benefits of increased throughput, reduced workload, and lower protein and reagent usage. This approach might be suitable for the pre-selection of viable formulations.

Objective: This study aimed to develop and evaluate ginsenoside Rg3 (GRg3)-loaded alginate/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as an oral drug delivery system with improved anticancer and antioxidant potential.

Significance: Despite its pharmacological promise, GRg3 suffers from poor solubility, instability, and low oral bioavailability. Encapsulation in biopolymeric NPs may overcome these barriers by enhancing stability and providing controlled release.

Methods: GRg3-loaded alginate/PLGA NPs were synthesized and characterized for size, stability, rheology, and release kinetics. Antiproliferative activity, cell cycle effects, and apoptosis markers were assessed in PC-3 prostate cancer cells. In vivo safety and antioxidant effects were evaluated in healthy rats using biochemical assays and histopathological analysis of liver and kidney tissues.

Results: The NPs had a mean diameter of ∼200 nm with shear-thinning behavior. GRg3 release followed a sustained pattern, best fitting the Korsmeyer-Peppas model with anomalous transport. In vitro, the formulation inhibited PC-3 cell proliferation in a concentration- and time-dependent manner, induced G0-G1 arrest, and elevated caspase-3 activity within 6 h. In vivo, oral administration caused no significant hepatic or renal alterations, and histopathology showed no inflammation or necrosis. GRg3 also reduced malondialdehyde levels, confirming antioxidant activity.

Conclusions: Encapsulation of GRg3 in alginate/PLGA NPs enhanced its stability, anticancer activity, and antioxidant potential without systemic toxicity. These findings highlight the promise of GRg3-loaded nanocarriers for cancer therapy, warranting further evaluation in disease-specific models.