Assay and drug development technologies最新文献

Continuous drug delivery modification is the scientific approach and is a basic need for the efficient therapeutic efficacy of active drug molecules. Polymer-drug conjugates have long been a hallmark of the drug delivery sector, with various conjugates on the market or in clinical trials. Improved drug solubilization, extended blood circulation, decreased immunogenicity, controlled release behavior, and increased safety are the advantages of conjugating drugs to the polymeric carrier like polyethylene glycol (PEG). Polymer therapies have evolved over the last decade, resulting in polymer-drug conjugates with diverse topologies and chemical properties. Traditional nondegradable polymeric carriers like PEG and hydroxy propyl methacrylate have been clinically employed to fabricate polymer-drug conjugates. Still, functionalized polymer-drug conjugates are increasingly being used to increase localized drug delivery and ease of removal. Researchers have developed multifunctional carriers that can "see and treat" patients using medicinal and diagnostic chemicals. This review focused on the various conjugation approaches for attaching the doxorubicin to different polymers to achieve enhanced therapeutic efficacy, that is, increased bioavailability and reduced adverse effects.

A highly selective, sensitive, rugged, and rapid ultra high-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) is optimized and validated for reliable quantification of atorvastatin (ATR) and its active metabolites, 2-hydroxy atorvastatin (2-ATR) and 4-hydroxy atorvastatin (4-ATR) in human plasma using atorvastatin-D5 (ATR-D5), 2-hydroxy atorvastatin-D5 (2-ATR-D5), and 4-hydroxy atorvastatin-D5 (4-ATR-D5) as deuterium-labeled internal standards (ISTDs), respectively. Isocratic mode chromatographic separation was used with a reverse-phase C₁₈ Symmetry Shield (150 × 4.6 mm, 5.0 μm) column and a mobile phase of acetonitrile:2 mM ammonium formate (pH-3.0) [65:35%v/v] at a flow rate of 0.7 mL/min. Electrospray ionization technique with positive ion mode polarity was applied to achieve the best signal intensity and stable response. Solid-phase extraction by direct elution method was applied to extract the drugs from the plasma sample. The calibration curve range was validated from a concentration range of 0.500-250 ng/mL for ATR and 2-ATR and 0.200-20 ng/mL for 4-ATR. The within-batch and between-batch precision and accuracy were found to be consistent and reproducible for all the analytes across the validation. Extraction recoveries were >80% for all analytes and ISTDs. All peaks of analytes and the respective ISTDs were eluted within 5.2 min. In this validated method, selective multivariate analytical approaches were utilized such as best fit linearity range for different strength formulations, preventive measures for in vivo and ex vivo autodegradation of metabolites, and shorter analysis time. This validated method can be useful for challenging quantification of ATR and its active metabolites for therapeutic drug monitoring and in high-throughput clinical study sample analysis.

The current pharmaceutical manufacturing scenario involves different techniques for the processing of materials. For example, the extraction unit is one of the essential aspects of plant-based pharmaceuticals. Recently, various kinds of extraction techniques have been used for analytical and preparative scales; among them, a supercritical fluid extractor (SCFE) is the most widely used technique for extraction. It is used for an extensive range of crude drugs and can be possible with the help of SCFE by varying temperature/pressure. Notably, it uses carbon dioxide (CO₂) for extraction instead of other solvents. Simultaneously, lyophilization is an important technique used at different processing steps along with other methods. In lyophilization, CO₂ is used as a cooling agent in the shelves of lyophilized equipment. It behaves as a supercritical fluid at critical pressure (Pc) of 72.7 atm and critical temperature (Tc) of 31°C. Considering the criteria mentioned earlier, there is a possibility that liquid CO₂ or supercritical carbon dioxide (SC-CO₂) can be used as a cooling agent in a lyophilizer and extraction solvent in SCFE. This review presents a brief outline for the possible validation parameters of the proposed novel processor; that is, SCFE/Dryer combo instrument containing Design Qualification, Installation Qualification, Operational Qualification, and Performance Qualification.

The research work was aimed to formulate and evaluate gastroretentive mucoadhesive film of calcium channel blocker, Lacidipine for treatment of gastroparesis. Box-Behnken design was used for preparation of optimized formulation using solvent casting method. In this design, different concentrations of mucoadhesive polymers HPMC E15, Eudragit RL100, and Eudragit RS100 were considered as independent variables and its effect on responses like percent drug release, swelling index at 12 h, and folding endurance of the film were examined. Drug and polymer compatibility studies were performed using Fourier transform infrared spectroscopy and differential scanning calorimetry. Optimized formulation was evaluated for organoleptic properties, weight variation, thickness, swelling index, folding endurance, drug content, tensile strength, percent elongation, drug release, and percent moisture loss. The results revealed that the film possessed considerable flexibility and smoothness, and in vitro drug release was found to be 95.22% ± 0.93% at the end of 12 h. Scanning electron microscopy imaging of film displayed smooth, uniform, and porous surface texture. The dissolution followed Higuchi's model and Hixson Crowell model displayed non-Fickian drug release mechanism. Furthermore, the film was incorporated in capsule and the presence of capsule showed no effect on the drug release profile. In addition, no change was observed in the appearance, drug content, swelling index, folding endurance, and drug release upon storage at 25°C ± 2°C and 60% ± 5% relative humidity for 3 months. Collectively, the study revealed that gastroretentive mucoadhesive film of Lacidipine could serve as an effective and alternate site-specific targeted delivery in the management of gastroparesis.

Antagonists of the serotonin receptor 2B (5-HT_2B) have shown great promise as therapeutics for the treatment of pulmonary arterial hypertension, valvular heart disease, and related cardiopathies. Herein, we describe a high-throughput screen campaign that led to the identification of highly potent and selective 5-HT_2B antagonists. Furthermore, selected compounds were profiled for their predicted ability to cross the blood-brain barrier. Two exemplary compounds, VU0530244 and VU0631019, were predicted to have very limited potential for brain penetration in human subjects, a critical profile for the development of 5-HT_2B antagonists devoid of centrally-mediated adverse effects.

Low water solubility is the main hindrance in the growth of pharmaceutical industry. Approximately 90% of newer molecules under investigation for drugs and 40% of novel drugs have been reported to have low water solubility. The key and thought-provoking task for the formulation scientists is the development of novel techniques to overcome the solubility-related issues of these drugs. The main intention of present review is to depict the conventional and novel strategies to overcome the solubility-related problems of Biopharmaceutical Classification System Class-II drugs. More than 100 articles published in the last 5 years were reviewed to have a look at the strategies used for solubility enhancement. pH modification, salt forms, amorphous forms, surfactant solubilization, cosolvency, solid dispersions, inclusion complexation, polymeric micelles, crystals, size reduction, nanonization, proliposomes, liposomes, solid lipid nanoparticles, microemulsions, and self-emulsifying drug delivery systems are the various techniques to yield better bioavailability of poorly soluble drugs. The selection of solubility enhancement technique is based on the dosage form and physiochemical characteristics of drug molecules.

Liposomes are unique novel drug delivery carriers that favor the effective transportation of pharmaceuticals. These vesicles acquire one or more phospholipid bilayer membranes, and an inner aqueous core can carry both aqueous and lipid drugs. While hydrophilic molecules can be confined in the aqueous core, hydrophobic molecules are injected into the bilayer membrane. Liposomes have many benefits as a drug delivery method, including biocompatibility, the capacity to carry large drug payloads, and a variety of physicochemical and biological parameters that can be altered to influence their biological characteristics. In addition, being a size of 10-100 nm range can have numerous additional benefits, including enhanced pharmacokinetics, clever escape from the reticuloendothelial system, greater in vivo stability, longer and site-specific administration, and increased internalization in tumor tissue (enhanced permeability and retention impact). The current review focuses on the structural composition of liposomes, formulation technologies, and suitable case studies for optimizing biopharmaceutical performance. Moreover, clinical trials and marketed formulations of liposomes have been also stated in the prior art.

Poorly soluble drug molecules/phytoconstituents are still a growing concern for biopharmaceutical delivery in the body. Polymeric micelles are the amphiphilic block copolymers and have been widely investigated as targeted nanocarriers for the treatment of various ailments. The versatility of nanocarriers is the self-assembling properties in the aqueous medium and forms a stable isotropic system in vivo. The hydrophobic core-hydrophilic shell configuration of the polymers used to the mixed micelles makes easy encapsulation of hydrophobic and hydrophilic drugs into the core. Polymeric micelles can also be combined with targeting ligands that increase their uptake by specific cells, decreasing off-target effects, and provide enhanced therapeutic effect. In the present review, we primarily focused on a critical appraisal of Polymeric micelles along with the method of preparation, mechanism of micelle formulation, and the ongoing formulations under clinical trials. In addition, the biological applications of this isotropic nanocarrier have been duly presented in each route of administration along with suitable case studies.

Drug absorption is improved by the intranasal route's wide surface area and avoidance of first-pass metabolism. For the treatment of central nervous system diseases such as migraine, intranasal administration delivers the medication to the brain. The study's purpose was to develop an in situ nasal hydrogel that contained liposomes that were loaded with sumatriptan succinate (SS). A thin-film hydration approach was used to create liposomes, and a 3² factorial design was used to optimize them. The optimized liposomes had a spherical shape, a 171.31 nm particle size, a high drug encapsulation efficiency of 83.54%, and an 8-h drug release of 86.11%. To achieve in situ gel formation, SS-loaded liposomes were added to the liquid gelling system of poloxamer-407, poloxamer-188, and sodium alginate. The final product was tested for mucoadhesive strength, viscosity, drug content, gelation temperature, and gelation time. Following intranasal delivery, in vivo pharmacokinetic investigations showed a significant therapeutic concentration of the medication in the brain with a C_max value of 167 ± 78 ng/mL and an area under the curve value of 502 ± 63 ng/min·mL. For SS-loaded liposomal thermosensitive nasal hydrogel, significantly higher values of the nose-to-brain targeting parameters, that is, drug targeting index (2.61) and nose-to-brain drug direct transport (57.01%), confirmed drug targeting to the brain through the nasal route. Liposomes containing thermosensitive in situ hydrogel demonstrated potential for intranasal administration of SS.