A comprehensive review on ecology, life cycle and use of Tecoma stans (bignoneaceae).

Tecoma stans is a widely distributed tall ornamental shrub in the plains of Indian subcontinent and is considered an invasive species across Argentina, Australia, South Africa, Pacific Islands and tropical regions of Asia. Besides having an ornamental significance, T. stans has been extensively investigated for its pharmaceutical applications as a source of bioactive compounds. In addition, the shrub is cultivated commercially as a potted flowering plant. We believe that T. stans, being a hardy, invasive and aggressively growing species, holds a considerable potential and a promising solution for re-greening waste and degraded lands outside its invasive range, due to its wider adaptability and drought tolerant characteristics. The shrub is an excellent source of pollen and nectar, that attracts diverse insect-pollinators and several species of birds. The prudent plantation of this shrub has the potential to restore the ecology of barren landscapes, that can change its perspective of 'being invasive' to 'being ecologically healthy' across the tropical, semi-arid and subtropical regions worldwide. This paper reviews the current updates on ecology, life cycle including morphology, plant growth characteristics, flowering phenology, reproductive biology, breeding system and fruiting of T. stans. In addition, details on insect-pollinator diversity and natural regeneration potential have also been discussed, besides highlighting its therapeutic and landscape use.

A systematic review and meta-analysis of serum and plasma cortisol levels in depressed patients versus control.

Depression is associated with hyperactivity of the hypothalamo pituitary adrenal axis. Cortisol is a steroid hormone, released from the adrenal gland and is considered to be a biological marker of stress and anxiety. Serum or plasma cortisol levels have been previously studied in depressive patients but reported contradictory results. The present meta analysis aims to assess the serum or plasma concentration of cortisol in depressive patients compared with controls. We have conducted a systematic review with sequential meta analysis according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Web of Science, PubMed, Scopus, and PsycINFO databases, and published reference lists were searched up to January 2021. We have conducted a systematic review on PubMed for the following search (MeSH) terms ("Hydrocortisone"[Mesh]) AND "Depressive Disorder"[Mesh]). The RevMan 5.3 and Open Meta Analyst software was used with the standard mean difference (SMD) and 95% confidence intervals (CIs). The Jamovi and Open Meta Analyst Software were used to evaluate the publication bias, sensitivity analysis, and meta regression as possible sources of heterogeneity. Seventeen studies having a combined population (n) of 1400 (743 depressive patients and 657 controls) had satisfied the inclusion criteria for serum or plasma cortisol. The pooled SMD of the serum or plasma cortisol levels in depressive patients compared with controls was 1.18, (95% CI: 0.84, 1.52; P < 0.00001) with I2 = 85% (Ph < 0.00001). This meta analysis indicates a statistically significant mean difference in serum or plasma cortisol between depressed patients and controls. Meta analysis concluded that serum or plasma cortisol can differentiate depressed patients from nondepressed controls.

Controlled-release injectable microemulsions: recent advances and potential opportunities.

INTRODUCTION: Controlled-release injectable (CRI) formulations hold significant value for several indications. However, there have been very few successful developments and approvals due to various challenges that include limited polymer options, drug-excipient process incompatibility and complex scale-up/validation processes. Microemulsion technology, as reviewed in this article, promises to resolve many of these challenges. AREAS COVERED: In addition to its development and manufacturing advantages, feasibility to engineer microemulsion formulations by choosing its constituents and nature of formulation vis-à-vis drug candidate demonstrates capability of microemulsion to modulate in-vivo drug release and thereby optimize drug pharmacokinetics and pharmacodynamics. This potential of microemulsion has been used in a few studies to prolong in vivo drug residence time resulting in a more favorable benefit/risk profile for various drugs. Virtues of injectable microemulsion, results related to prolonged-release injectable microemulsion, impact on drug safety and efficacy and possible opportunities have been discussed. A detailed review of research work on microemulsions as well as other parenteral controlled-release formulations was conducted using PubMed, Science Direct and Google Scholar. EXPERT OPINION: The fact that microemulsion formulations administered through subcutaneous or intramuscular route would undergo significantly prolonged elimination should be leveraged to develop novel CRI drug products. Such products will find enormous application for several drug candidates which have poor oral pharmacokinetics resulting into poor treatment outcome.

Bioequivalence challenges in development of fixed-dose combination products: looking beyond reformulation.

INTRODUCTION: Bioequivalence study is a critical step in the development of novel fixed-dose combination products (FDCPs). While bioequivalence of prototype FDCP to the approved monocomponent products facilitates speedier development and approval, lack of bioequivalence often leads to development delays due to reformulation. AREAS COVERED: Pharmacokinetic (PK) interaction is one of those issues that often have the potential to completely derail the product development process. The objective of the present article is to highlight PK challenges along with strategies to resolve them. EXPERT OPINION: A rationale development approach that integrates formulation and clinical insight, so as to understand the clinical significance of non-bioequivalence, would help to minimize the development timeline. While bioequivalence should always be the initial goal in the formulation development, failure to meet it should not immediately lead to reformulation. Instead, evaluating the PK of actives in FDCPs in approved market products, and their consequent clinical implications, would help to make rationale and pragmatic decisions. Such an approach will facilitate the initiation of clinical studies, without increasing the risk of failing to meet safety and efficacy end points, and in turn will significantly improve the productivity.

Ketorolac tromethamine transdermal gel: development, in vitro and in vivo evaluation.

The authors developed and evaluated a transdermal gel formulation of ketorolac tromethamine (ketorolac) for the treatment of nociceptive somatic pain. The formulation was optimized for skin permeation enhancers, pH of the system, and dosage strength using in vitro and in vivo techniques. Of the various permeation enhancers evaluated, dimethyl sulfoxide (DMSO) and oleic acid were found to significantly increase skin permeation flux of ketorolac. The concentration of DMSO affected the rate as well as extent of transdermal absorption. Use of citric acid further improved the skin penetration of ketorolac. In vitro diffusion results indicated significant increase in drug permeation with increasing drug concentration. However, the same did not translate into higher skin permeation during in vivo study. Although the area under concentration time curve (AUC(0-t)) increased significantly with increasing dose, the effect on maximum serum concentration (C(max)) was insignificant. The formulation can be used for inflammatory pain management while avoiding gastric adverse events associated with oral ketorolac.

Optimizing delivery of flurbiprofen to the colon using a targeted prodrug approach.

The carboxylic group responsible for the gastric side-effects of the propionic acid derivative, flurbiprofen, was masked temporarily to overcome these side-effects and to accomplish colon-specific delivery of the drug. An amide prodrug (FLU-GLY) was synthesized by coupling flurbiprofen with L-glycine. Confirmation and characterization of the structure of the synthesized prodrug included elemental analysis, Fourier transform (FT)-IR, FT-NMR, mass (FAB) spectroscopy, and determinations of R(f), R(t) and R(M) values, respectively. Aqueous solubility and lipophilicity (logP) value were determined at pH 1.2, 4.0, 6.8 and 7.4. In-vitro reversion of FLU-GLY to flurbiprofen was measured at different pHs and in a simulated colonic environment. Acute toxicity and ulceration potential were evaluated in-vivo in albino rats. Pre-formulation studies showed increased hydrophilicity but a non-significant increase in lipophilicity of the prodrug. In-vitro reversion studies suggested that the prodrug remained intact until colonic pH was attained, when the colonic microfloral enzymes (amidase) hydrolysed the FLU-GLY amide linkage, releasing the free drug. In-vivo evaluation indicated that the prodrug was much less toxic and had less ulcerogenic activity than the parent drug. Selective delivery of drugs to the colon can be useful in terms of reducing the dose administered and reducing undesirable side-effects.

Two-stage optimization process for formulation of chitosan microspheres.

The objective of the present study was to optimize the concentration of a chitosan solution, stirring speed, and concentration of drugs having different aqueous solubility for the formulation of chitosan microspheres. Chitosan microspheres (unloaded and drug loaded) were prepared by the chemical denaturation method and were subjected to measurement of morphology, mean particle size, particle size distribution, percentage drug entrapment (PDE), drug loading, and drug release (in vitro). Morphology of the microspheres was dependent on the level of independent process parameters. While mean particle size of unloaded microspheres was found to undergo significant change with each increase in concentration of chitosan solution, the stirring rate was found to have a significant effect only at the lower level (ie, 2000 to 3000 rpm). Of importance, spherical unloaded microspheres were also obtained with a chitosan solution of concentration less than 1 mg/mL. Segregated unloaded microspheres with particle size in the range of 7 to 15 microm and mean particle size of 12.68 microm were obtained in the batch prepared by using a chitosan solution of 2 mg/mL concentration and stirring speed of 3000 rpm. The highest drug load ( microg drug/mg microspheres) was 50.63 and 13.84 for microspheres containing 5-fluorouracil and methotrexate, respectively. While the release of 5-fluorouracil followed Higuchi's square-root model, methotrexate released more slowly with a combination of first-order kinetics and Higuchi's square-root model. The formation of chitosan microspheres is helped by the use of differential stirring. While an increase in the concentration of water-soluble drug may help to increase PDE and drug load over a large concentration range, the effect is limited in case of water-insoluble drugs.

Poly(D,L-lactide-co-glycolide) microspheres containing 5-fluorouracil: optimization of process parameters.

The objective of this research was to optimize the processing parameters for poly(D,L-lactide-co-glycolide) (PLGA) microspheres of 5-fluorouracil (5-FU) and to mathematically relate the process parameters and properties of microspheres. Microspheres were prepared by a water-in-oil-in-water emulsion solvent evaporation technique. A 3(2) factorial design was employed to study the effect of the volume of the internal phase of the primary emulsion and the volume of the external phase of the secondary emulsion on yield, particle size, and encapsulation efficiency of microspheres. An increase in the volume of the internal phase of the primary emulsion resulted in a decrease in yield and encapsulation efficiency and an increase in particle size of microspheres. When the volume of the external phase of the secondary emulsion was increased, a decrease in yield, particle size, and encapsulation efficiency was observed. Microspheres with good batch-to-batch reproducibility could be produced. Scanning electron microscopic study indicated that microspheres existed as aggregates.