Drug Development and Industrial Pharmacy最新文献

Objective: This study aims to investigate the quality consistency between traditional decoction (TD) of Amomum villosum and its dispensing granule decoction (DGD). Fifteen batches of TD and nine batches of dispensing granules (manufactured by A, B, and C) were prepared and evaluated for their consistency.

Methods: Firstly, The chemical similarity of TD and DGD was examined using GC and HPLC, coupled with hierarchical cluster analysis (HCA), criteria importance though intercrieria correlation(CRITIC) weighting method, and principal component analysis (PCA). Secondly, the gastrointestinal motility experiments in mice, along with the CRITIC weighting method, were employed to assess the bioequivalence of TD and DGD of Amomum villosum. Finally, the entropy weight technique-gray relative analysis(GRA) method was used to compare the quality of Amomum villosum decoctions.

Results: ①The CRITIC weighting method indicated significantly higher scores for TD than DGD (p < 0.01). HCA and PCA results demonstrated a clear distinction between TD and DGD. ②Gastrointestinal motility test results revealed no significant difference between TD and DGD in other indicators (p > 0.05).③Gray relative analysis results showed that the relative correlation of TD was more significant than that of DGD.

Conclusion: The chemical composition of DGD and TD differed. The biological activity of DGD-A/B was consistent with that of TD, while the difference between DGD-C and TD was significant. A comprehensive evaluation showed that TD exhibited better quality than DGD. DGD manufacturers should optimize the preparation process to enhance product quality.

Objective: Glioma is the most common and deadly primary malignant tumor in adults. Treatment outcomes are ungratified due to the presence of blood-brain barrier (BBB), glioma stem cells (GSCs) and multidrug resistance (MDR). Docetaxel (DTX) is considered as a potential drug for the treatment of brain tumor, but its effectiveness is limited by its low bioavailability and drug resistance. Tetrandrine (TET) reverses the resistance of tumor cells to chemotherapy drugs. Borneol (BO) modified in micelles has been shown to promote DTX plus TET to cross the BBB, allowing the drug to better act on tumors. Therefore, we constructed BO-modified DTX plus TET micelles to inhibit chemotherapeutic drug resistance.

Significance: Provide a new treatment method for drug-resistant brain gliomas.

Methods: In this study, BO-modified DTX plus TET micelles were prepared by thin film dispersion method, their physicochemical properties were characterized. Its targeting ability was investigated. The therapeutic effect on GSCs was investigated by in vivo and in vitro experiments.

Results: The BO-modified DTX plus TET micelles were successfully constructed by thin film dispersion method, and the micelles showed good stability. The results showed that targeting micelles increased bEnd.3 uptake and helped drugs cross the BBB in vitro. And we also found that targeting micelles could inhibit cell proliferation, promote cell apoptosis and inhibit the expression of drug-resistant protein, thus provide a new treatment method for GSCs in vitro and in vivo.

Conclusions: BO-modified DTX plus TET micelles may provide a new treatment method for drug-resistant brain gliomas.

Objectives: Glimepiride Orodispersable Tablets (ODT) were prepared with the goal to have rapid onset of action and higher bioavailability with ease administration to individuals with swallowing difficulty to ameliorate patient compliance.

Significance: Glimepiride is a contemporary hypoglycemic medication that belongs to the family of sulfonylurea derivatives. It is used in type 2 diabetes mellitus. Compliance adherence remains one of the limitations with the conventional drug delivery system especially in pediatric, geriatric, psychiatric, and traveling patients, for such population ODT provides a good alternate dosage form compared with Commercial Tablets.

Method: The Comparative in vivo pharmacokinetic parameters of the prepared ODT and conventional tablets (CT) were evaluated using an animal model. The plasma concentration of Glimepiride after oral administration of a single dose was determined at predetermined time intervals with HPLC. The pharmacokinetic parameters were calculated using PK Solutions 2.0 from Summit PK® software.

Results: The Cmax obtained with ODT (22.08 µg/ml) was significantly (p = 0.006) high, a lower tmax of 3.0 hr was achieved with the orodispersable formulation of the drug. The ODT showed 104.34% relative bioavailability as compared to CT and left shift of tmax as well.

Conclusion: As per findings of the in vivo investigation, the Glimepiride ODT would be beneficial in terms of patient compliance, quick onset of action, and increased bioavailability.

Introduction and purpose: The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 - 7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO₂. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer.

Methods: A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO₂) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors.

Results: The use of the supercritical technique at 40 °C and 10 MPa for 2 h allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin's bitter taste.

Conclusions: Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients.

Objective: The aim of this study is to demonstrate the effect of stoichiometry upon characteristics of quercetin-arginine (QCT-Arg) cocrystals.

Significance: Quercetin (QCT) is a most abundant flavonoid in vegetables and fruits and has been widely used as an antioxidant. However, its oral bioavailability remains low due to poor aqueous solubility. We illustrate that QCT-Arg cocrystals formulated through an optimized stoichiometry can be a useful approach for its solubilization.

Method: Cocrystals were prepared using solvent evaporation method. Characterizations were performed through microscopic, spectroscopic, and thermal techniques. The stoichiometry was confirmed from the binary phase diagram which was prepared using thermograms derived from differential scanning calorimetric experiments.

Result: Cocrystal formation was accompanied by the conversion of isotropic phase into anisotropic one. Thread-like cocrystals were formed, regardless of QCT-Arg stoichiometry and solvent's polarity. Spectral analyses suggested that cocrystal structure was held together by hydrogen bonding between QCT and Arg. We ruled out the existence of eutectic mixture based on the observation of two eutectic points in the binary phase diagram.

Conclusion: Morphology of cocrystals remained unaffected by the solvent type, stoichiometry and the presence of surfactant. We noticed that the cocrystals could improve the aqueous solubility of QCT.

Background: Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects.

Methods: Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX).

Results: Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC₅₀ = 1.4 μM) more than MCF-7/ADR cells (IC₅₀ = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC₅₀ = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC₅₀ = 7.2 μM) and SN (IC₅₀ = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC₅₀ from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC₂₀) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression.

Conclusions: Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.

Objective: The present work aims to develop mucoadhesive thermosensitive nasal in situ gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form.

Significance: Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive in situ gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability.

Method: In-situ gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X₁) as gelling agent and hydroxypropyl methyl cellulose K4M (X₂) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and ex-vivo diffusion. Central composite design (CCD) was adopted for optimization.

Result: Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months.

Conclusion: It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive in situ gel has potential to increase drug bioavailability.

Introduction: Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouthfeel suitable for direct compression is limited.

Objective: This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs.

Methods: A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation.

Results: The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% microcrystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min.

Conclusion: Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications.

Objective: To use Raman Spectroscopy for qualitative and quantitative evaluation of pharmaceutical formulations of active pharmaceutical ingredient (API) of Cephalexin.

Significance: Raman Spectroscopy is a noninvasive, nondestructive, reliable and rapid detection technique used for various pharmaceutical drugs quantification. The present study explores the potential of Raman Spectroscopy for quantitative analysis of pharmaceutical drugs.

Method: For qualitative and quantitative analysis of Cephalexin API, various standard samples containing less and more concentration of API than commercial tablet was prepared. To study spectral differences, the mean plot of all the samples was prepared. For qualitative analysis, Principal Component Analysis (PCA) and for quantitative analysis Partial Least Square Regression analysis (PLSR) was used. Both of these are Multivariate data analysis techniques and give reliable results as published in previous literature.

Results: PCA model distinguished all the Raman Spectral data related to the various Cephalexin solid dosage formulations whereas the PLSR model was used to calculate the concentration of different unknown formulations. For the PLSR model, RMSEC and RMSEP were determined to be 3.3953 and 3.8972, respectively. The prediction efficiency of this built PLSR model was found to be very good with a goodness of the model value (R²) of 0.98. The PLSR model also predicted the concentrations of Cephalexin formulations in the blind or unknown sample.

Conclusion: These findings demonstrate that the Raman spectroscopy coupled to PLSR analysis could be regarded as a fast and effectively reliable tool for quantitative analysis of pharmaceutical drugs.

Aim: The primary objective of the research was to develop a cubosomal in situ gel encapsulated with Triamcinolone acetonide (TCA) in order to enhance its penetration through the blood-brain barrier (BBB) when administered via the intranasal route, thus enabling efficient and rapid action.

Method: Cubosomes were formulated by top-down approach using glyceryl monooleate (GMO), using pluronics127 (PF127) and polyvinyl alcohol (PVA) in varying proportions based on the Box-Behnken design. High resolution transmission electron microscopy (HR-TEM) analysis confirmed the morphology of the cubosomes. The in situ gel was formulated and optimized. Experiments involving ex vivo permeation and histopathology analyses were undertaken to evaluate drug permeation and tissue effects.

Results: The cubosomes exhibited a particle size (PS) of 197.9 nm, zeta potential (ZP) of -31.11 mV, and entrapment efficacy (EE) of 84.31%, with low deviation. Batch F4 (19% PF127) showed favorable results. In vitro and ex vivo permeation studies revealed drug release of 78.59% and 76.65%, respectively, after 8 h. Drug release followed the Hixson Crowell model of release kinetics. The histopathological examination revealed no signs of toxicity or adverse effects on the nasal mucosa of the sheep. The formulation exhibited short-term stability, maintaining its integrity and properties when stored at room temperature.

Conclusion: The utilization of an intranasal cubosomal in situ gel encapsulated with TCA was anticipated to lower intracranial pressure and improve patient adherence by offering effective relief for individuals suffering from Brain edema. This efficacy is attributed to its rapid onset of action and its safe and well-tolerated dosage form.