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Self-emulsifying drug delivery systems (SEDDS) can increase the solubility and bioavailability of poorly soluble drugs. The inability of 35% to 40% of new pharmaceuticals to dissolve in water presents a serious challenge for the pharmaceutical industry. As a result, there must be dosage proportionality, considerable intra- and inter-subject variability, poor solubility, and limited lung bioavailability. As a result, it is critical that drugs intended for oral administration be highly soluble. This can be improved through a variety of means, including salt generation and the facilitation of solid and complicated dispersion. Surfactants, lubricants, and cosolvents may occasionally be found in SEDDS or isotropic blends. Lipophilic drugs, whose absorption is limited by their dissolution rate, have been used to demonstrate the effectiveness of various formulations and techniques. These particles can form microemulsions and suitable oil-inwater emulsions with minimal agitation and dilution by the water phase as they pass through the gastrointestinal tract. This study summarises the numerous advances, biopharmaceutical components, variations, production techniques, characterisation approaches, limitations, and opportunities for SEDDS. With this context in mind, this review compiles a current account of biopharmaceutical advancements, such as the application of quality by design (QbD) methodologies to optimise drug formulations in different excipients with controllable ratios, the presence of regulatory roadblocks to progress, and the future consequences of SEDDS, encompassing composition, evaluation, diverse dosage forms, and innovative techniques for in vitro converting liquid SEDDS to solid forms.
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Coming to the edge of disease manufacturing in the twenty-first-century, breast cancer occupies a terrifying scenario in the globe, especially in adult women. Its curiosity endeavours remarkable advances made during the past decennaries for cancer treatment and diagnosis.
It accounts for the fifth leading cause of transience, killing approximately 570,000 people per annum. To reduce the prognosis of clinical oncological development with the application of a new chemical entity, some of the critical challenges, like active pharmaceutical ingredients with high chemical resistance, extreme side effects, and high treatment costs are some of the limitations in the curbing aspects of breast melanoma. In cancer research, hence, the development of drugs that are safe, efficient, and cost-effective remains a 'Holy Grail' that may be considered as a boon to target the malignant tissues with novel therapeutics devices. Through the findings on overcoming the drawbacks of traditional methods, researchers have given special attention to cancer-preventive and theranostic approaches based on some novel drug delivery systems. The present study forecasts the wide-ranging modern applications, and on developing some novel liposomal drug delivery therapy against breast cancer.ABSTRACT
The current review intends to regulate and accurately evaluate genotoxic contaminants in drug substance and drug product method and formulation process development, validation, and degradation pathways. The Quality by Design (QbD) principles can be applied to the systematic evaluation and control of impurities enabled by the development of modern analytical techniques, including the performance of risk assessment, the screening of Critical Process Parameters (CPPs), and the identification of the most influential variables in the optimization of the evaluation and control methods. Current difficulties in removing genotoxic contaminants and the procedures for doing so have been outlined in this review, along with the steps necessary to acquire optimum techniques and the most acceptable formulations. In addition to this, division, characterization, assessment, quantification, and formation of genotoxic impurities sources and control strategy for genotoxic impurities, handling of nitrosamine assay content of drug products in different industrial methodologies and their chemometric prospects and associated recent patents are also explored.
Subject(s)
Drug Contamination , Drug Contamination/prevention & control , Risk AssessmentABSTRACT
Introduction: The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB) signaling. NF-κB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-α), and interleukin-1ß (IL-1ß). Although much research targeted the NF-κB and MMP9 signaling pathways, a subsequent investigation of target mediators in the inflammatory ulcer healing and NF-κB pathway has not been done. Methods: The docking studies of compounds TMF and EGCG were performed by applying PyRx and available software to understand ligand binding properties with the target proteins. The synergistic ulcer healing and anti-arthritic effects of MFS were elucidated using dextran sulfate sodium (DSS)-induced colon ulcer in Swiss albino rats. The colon mucosal injury was analyzed by colon ulcer index (CUI) and anorectic tissue microscopy. The IL-1ß, tumor necrosis factor (TNF-α), and the pERK, MMP9, and NF-κB expressions in the colon tissue were determined by ELISA and Western blotting. RT-PCR determined the mRNA expression for inflammatory marker enzymes. Results: The docking studies revealed that EGCG and TMF had a good binding affinity with MMP9 (i.e., -6.8 and -6.0 Kcal/mol) and NF-kB (-9.4 and 8.3 kcal/mol). The high dose MFS better suppressed ulcerative colitis (UC) and associated arthritis with marked low-density pERK, MMP9, and NF-κB proteins. The CUI score and inflammatory mediator levels were suppressed with endogenous antioxidant levels in MFS treated rats. Conclusion: The MFS effectively unraveled anorectic tissue inflammation and associated arthritis by suppressing NF-κB-mediated MMP9 and cytokines.
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Platelet-inspired nanoparticles have ignited the possibility of new opportunities for producing similar biological particulates, such as structural cellular and vesicular components, as well as various viral forms, to improve biocompatible features that could improve the nature of biocompatible elements and enhance therapeutic efficacy. The simplicity and more effortless adaptability of such biomimetic techniques uplift the delivery of the carriers laden with cellular structures, which has created varied opportunities and scope of merits like; prolongation in circulation and alleviating immunogenicity improvement of the site-specific active targeting. Platelet-inspired nanoparticles or medicines are the most recent nanotechnology-based drug targeting systems used mainly to treat blood-related disorders, tumors, and cancer. The present review encompasses the current approach of platelet-inspired nanoparticles or medicines that have boosted the scientific community from versatile fields to advance biomedical sciences. Surprisingly, this knowledge has streamlined to development of newer diagnostic methods, imaging techniques, and novel nanocarriers, which might further help in the treatment protocol of the various diseased conditions. The review primarily focuses on the novel advancements and recent patents in nanoscience and nanomedicine that could be streamlined in the future for the management of progressive cancers and tumor targeting. Rigorous technological advancements like biomimetic stem cells, pH-sensitive drug delivery of nanoparticles, DNA origami devices, virosomes, nano cells like exosomes mimicking nanovesicles, DNA nanorobots, microbots, etc., can be implemented effectively for target-specific drug delivery.
Subject(s)
Nanoparticles , Neoplasms , Humans , Drug Delivery Systems , Neoplasms/drug therapy , Nanoparticles/chemistry , Pharmaceutical Preparations , NanotechnologyABSTRACT
Objectives: The aim of the present work was to prepare QbD enabled optimization, and to improve the oral bioavailability of freeze-dried polymeric nanoparticles of cinacalcet hydrochloride manufactured by nanoprecipitation and ultrasonication methods using polymers PLGA, and poloxamer-188. Materials and Methods: The initial screening and optimization were carried out for the formulations by employing Taguchi and Box-Behnken Designs. The FT-IR and DSC revealed no interactions and had no incompatibility among the selected drug and polymers. The nanoparticles were characterized for % drug release, particle size analysis, zeta potential, PDI, SEM, TEM, P-XRD, TGA, DTA, in vitro, and in vivo drug release study. Results: In vitro drug release study showed sustained release of the drug from the optimized batch by diffusion mechanism. The optimized nanoparticle formulation was recognized by numerical and graphical methods using validation of the experimental model. The optimized batch was stable as per the ICH stability guidelines for 6 months with no considerable alternation noticed in particle size, entrapment efficiency, and in vitro drug release. The pharmacokinetic parameters of AUC and Cmax data for the optimized formulation increased 3- and 2.9-folds compared to the pure-drug suspension. Conclusion: The prepared polymeric nanoparticles formulation is an alternative delivery system for enhanced therapeutic efficacy and bioavailability potential of a model drug to manage long-term normocalcemia in patients with preliminary hyperparathyroidism.
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OBJECTIVES: Abiraterone acetate is a well-known anticancer drug and a steroidal derivative of progesterone for treatment of patients with hormone-refractory prostate cancer. Chemometrics-assisted reverse phase high performance liquid chromatography (RP-HPLC) development of the drug abiraterone acetate has been employed in this study using an analytical quality by design (AQbD) approach. MATERIALS AND METHODS: Drug separation was performed using a Princeton Merck-Hibar Purospher STAR (C18, 250 mm × 4.6 mm) i.d., 5 µm particle size) with ultraviolet detection at 235 nm. A Box-Behnken statistical experimental design with response surface methodology was executed for method optimization and desired chromatographic separation from its formulation with a few numbers of experimental trials. The impact of three independent variables, namely, composition of the mobile phase, pH, and flow rate, on response retention time and peak area was studied by constructing an arithmetic model from these variables. RESULTS: Optimized experimental conditions for the proposed work include the mobile phase acetonitrile and phosphate buffer (10 mM KH2PO4) (20:80 %v/v). At the concentration range of 2-100 µg/mL, a linear calibration curve was found. Recovery was performed at three concentrations and was foun to be between 98% and 102%. The 3D response surface curves revealed that mobile phase composition and flow rate were the most substantial critical factors affecting desired responses. CONCLUSION: An attempt has been made to develop and validate an economical, precise, robust, stability-indicating AQbD-based RP-HPLC method that can be employed successfully for the routine analysis of abiraterone acetate in quality control labs.
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Context: There is no straightforward method for estimating cinacalcet HCl in biological materials such as serum exists. As a result, the goal of this research is to develop a simple quality by design (QbD) enabled reverse phase-Ultra-Fast Liquid Chromatography (RP-UFLC) model for analyzing cinacalcet HCl in serum. Aim: The current study envisages the development and validation of an isocratic simple, precise, and rapid QbD enabled RP-UFLC method for the quantification of cinacalcet HCl in both solution form and blood samples. Subjects and Methods: The optimum conditions were outlined, selecting three influential factors (CMPs) i.e., mobile phase composition, flow rate, and injection volume. Systematic optimization was performed by 32-Box Benkhen experimental design using response surface methodology. The selected variables are further assessed for observed responses Critical Analytical attributes, i.e., peak area, retention time (Rt), USP Plate count. The optimized method used a chromatographic C18 (100 mm × 4.6 mm i.d) column with mobile phase (acetonitrile and Tetrabutyl Ammonium Hydrogen Sulphate [TBSH]) in the ratio of 1:1, with a flow rate of 1 mL/min with UV at λmax 223 nm. The developed method was found to be specific for cinacalcet HCl, enduring no interference of peaks with an overall analytical Rt of 4.3 min. Results: The Accuracy reported as % recovery was found to be 96.83%-101.32% and 95.18%-102.49% respectively. Inter-day precision (reproducibility) and intra-day precision (repeatability) were found to be 0.22-1.19 standard deviation (SD) and 0.14-2.12 SD respectively. The calibration curve was found to be linear with a regression equation Y = 195.8x + 21852, with R 2 0.999 over a concentration range from 100 to 100,000 ng/mL. Conclusion: The required detection and quantitation limits (Limit of Detection and Limit of Quantitation) values were obtained within the acceptance limit based on S/N ratio which indicates the method was sensitive and rapidity of the method. Further, the developed QbD enabled UFLC method was approved and effectively entreated the blood tests to study the pharmacokinetic parameters which indicate a robust, accurate cost-effective method intended for quality control tool for routine systematic analysis in research labs.
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OBJECTIVES: This research aimed to evaluate the antiangiogenic activity of isolated flavonoid 4a,5,8,8a-tetrahydro-5-hydroxy-3,7,8-trimethoxy-2-(3,4-dimethoxyphenyl) chromen-4-one (TMF) from Tabebuia chrysantha. STAT3-MMP9 signalling is a signal transduction mechanism that promotes angiogenesis in various cancers. METHODS: The tumour xenografting chicken embryo chorioallantoic membrane (CAM) model-based ex vivo assay was used to evaluate the activity of TMF. The Western blot, densitometric analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the activity of the MMP9. Zebrafish embryos were used to evaluate embryotoxicity, and in vitro free radical scavenging activity of flavonoid was also elucidated. KEY FINDINGS: This research assessed the high level of STAT3, p-ERK, VEGF-R and MMP9 in the tissue extract of the control group, and also, the suppression of angiogenesis in the treatment groups was due to scavenged ROS and RNS, dephosphorylation of STAT3 and ERK, and suppression of MMP9 gene expression. CONCLUSION: The isolated flavonoid named TMF from T. chrysantha functions as specific regulators of target proteins of angiosarcoma. The STAT3-MMP9 signalling may be used as an effective prognostic marker of angiosarcoma.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Hemangiosarcoma/drug therapy , Matrix Metalloproteinase 9/metabolism , STAT3 Transcription Factor/metabolism , Tabebuia , Animals , Cell Proliferation/drug effects , Chick Embryo , Chorioallantoic Membrane , Flavonoids/pharmacology , Plant Extracts/pharmacology , Signal Transduction/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Innovations in pharmaceutical research are striving for designing newer drug therapies to eradicate deadly diseases. Strategies for such inventions always flourish with keys and objectives of minimal adverse effects and effective treatment. Recent trends in pharmaceutical technology specify that mucoadhesive drug delivery system is particularly appropriate than oral control release, for getting local systematic delivery of drugs in GIT for an extended interval of time at a predetermined rate. However, it is somehow expensive and unpleasant sensation for some patients, but still it is needful for getting short enzymatic activity, simple administration without pain and evasion of fast pass metabolism. Usually the vehicles employed in drug delivery of mucoadhesive system have a significant impact that draws further attention to potential benefits like improved bioavailability of therapeutic agents, extensive drug residence time at the site of administration and a comparatively faster drug uptake into the systemic circulation. The drug release from mucoadhesive multiparticulates is contingent on several types of factors comprising carrier need to produce the multiparticles and quantity of medication drug contained in them. Mucoadhesion is characterized by selected theories and mechanisms. Various strategies emergent in mucoadhesive multiparticulate drug delivery system (MMDDS) by in-vitro as well as ex-vivo description and characterization are also critically discussed. Apart from these, the primary focus during this review is to highlight current patents, clinical status, and regulatory policy for enhancement of mucoadhesive multi-particulate drug delivery system in the present scenario.
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BACKGROUND: Quality by Design (QbD) is associated with a modern, systematic, scientific and novel approach which is concerned with pre-distinct objectives that not only focus on product, process understanding but also lead to process control. It predominantly signifies the design and product improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final products quality characteristics. It is quite essential to identify the desired and required product performance report, such as Target Product Profile, typical Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA). METHODS: This review highlighted the concepts of QbD design space, for critical material attributes (CMAs) as well as the critical process parameters that can totally affect the CQAs within which the process shall be unaffected thus, consistently manufacturing the required product. Risk assessment tools and design of experiments are its prime components. RESULTS: This paper outlines the basic knowledge of QbD, the key elements; steps as well as various tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized. CONCLUSION: This article provides a complete data as well as the roadmap for universal implementation and application of QbD for pharmaceutical products.
