Track topics on Twitter Track topics that are important to you
The objective of this study was to formulate an anticancer preclinical lead, IIIM-290, loaded in solid dispersions to enhance its solubility, dissolution, and oral pharmacokinetics. IIIM-290 is an in-house preclinical anticancer lead prepared by semisynthetic modification of the natural product rohitukine. It is an orally bioavailable Cdk inhibitor showing efficacy in xenograft models of pancreatic, colon and leukemia cancer. It demonstrated in vivo efficacy at a relatively higher dose owing to its poor aqueous solubility (∼8.6 µg/mL). Binary and ternary solid dispersions containing PVP K-30, xanthan gum, and PEG-PPG-PEG were selected after solubility screening of various hydrophilic polymers. Several formulations with varying ratios of polymers, alone and in combination, were prepared and investigated for their effects on the solubility enhancement of IIIM-290. The binary solid dispersion VKB-SD75, prepared with PVP K-30 at the ratio of 1:4 w/w, was identified as the optimized composition that displayed 17-fold improvement in the aqueous solubility of IIIM-290. VKB-SD75 was scaled up to a 100-g scale. IIIM-290 and VKB-SD75 were evaluated for DSC, p-XRD, FTIR, H NMR, SEM, in vitro dissolution, and oral pharmacokinetics, as well as for in vivo anticancer activity in the Ehrlich solid tumor model. The oral administration of VKB-SD75 in BALB/c mice resulted in a 1.9-fold improvement in plasma exposure. These findings also correlated well when the formulation was administered to mice in the Ehrlich solid tumor model. The newly developed solid dispersion is expected to reduce the dose of IIIM-290 by ∼40-50% in preclinical and clinical studies.
This article was published in the following journal.
Name: International journal of pharmaceutics
The CXCR4/CXCL12 axis plays prominent roles in tumor metastasis and inflammation. CXCR4 has been shown to be involved in a variety of inflammation-related diseases. Therefore, CXCR4 is a promising pot...
Complex amorphous solid dispersions based on poly(2-hydroxyethyl methacrylate): study of drug release from a hydrophilic insoluble polymeric carrier in the presence and absence of a porosity increasing agent.
Amorphous solid dispersions are nowadays typically made up of a drug compound and a water-soluble polymer. However, recently it has been demonstrated that amorphous solid dispersions based on insolubl...
Several drugs are pH-dependent soluble weak bases with a poor solubility in the intestinal pH range. Additionally a variable gastric pH, which is a common issue in the population, potentially reduces ...
In this study, the time-dependent evolution of amorphous probucol nanoparticles was characterized by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). The nanopa...
Amorphous solid dispersions (ASDs) are found to be a well-established strategy for overcoming limited aqueous solubility and poor oral bioavailability of active pharmaceutical ingredients (APIs). One ...
To obtain evidence of antitumor effect of CX-072 in combination with anticancer therapy in adult patients with solid tumor based upon overall response rate by Response Evaluation Criteria ...
The purpose of this study is to establish the recommended Phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-101 in combi...
This study is to investigate the bioavailability of a hot-melt extruded amorphous solid dispersion formulation of Efavirenz compared to a marketed formulation(Stocrin®).
This is an open-label study to evaluate the safety and efficacy of an anticancer medication (A01) with immune cells (IC01) in subjects with advanced solid tumors.
This is an open label, Phase 1b/2 study with multiple treatment arms evaluating the safety, tolerability, PK, and preliminary efficacy of rucaparib in combination with a second anticancer ...
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Injury to the nervous system secondary to exposure to lead compounds. Two distinct clinical patterns occur in children (LEAD POISONING, NERVOUS SYSTEM, CHILDHOOD) and adults (LEAD POISONING, NERVOUS SYSTEM, ADULT). In children, lead poisoning typically produces an encephalopathy. In adults, exposure to toxic levels of lead is associated with a peripheral neuropathy.
Poisoning that results from chronic or acute ingestion, injection, inhalation, or skin absorption of LEAD or lead compounds.
Unstable isotopes of lead that decay or disintegrate emitting radiation. Pb atoms with atomic weights 194-203, 205, and 209-214 are radioactive lead isotopes.
Neurologic disorders occurring in children following lead exposure. The most frequent manifestation of childhood lead toxicity is an encephalopathy associated with chronic ingestion of lead that usually presents between the ages of 1 and 3 years. Clinical manifestations include behavioral changes followed by lethargy; CONVULSIONS; HALLUCINATIONS; DELIRIUM; ATAXIA; and vomiting. Elevated intracranial pressure (HYPERTENSION, INTRACRANIAL) and CEREBRAL EDEMA may occur. (From Adams et al., Principles of Neurology, 6th ed, p1210-2)
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...