Drug polymorphism: a review

Formulators are charged with the responsibility of formulating a product which is physically and chemically stable, and bioavailable. Solid-state properties including polymorphism, solvate and salt formation can have a profound impact on important properties (solubility & stability) that are essential for successful development of drug candidates. Crystallization of pharmaceutically active ingredients, particularly those that possess multiple polymorphic forms, are among the most critical and least understood pharmaceutical manufacturing processes. Many process and product failures can be traced to a poor understanding and control of crystallization processes. Most drugs exhibits structural polymorphism and it is desirable to develop the most thermodynamically stable polymorph of the drug to assure reproducible bioavailability of the product over its shelf-life under a variety of real world storage conditions. There are occasional situations in which development of a meta-stable crystalline or amorphous form is justified to achieve the desired medical benefit. Such situation includes those in which faster dissolution rates or higher concentrations are desired in order to achieve rapid absorption and the efficiency or to achieve acceptable systemic exposure for low solubility drugs. This article briefly reviews the basic principle of polymorphism, different classes of phase transformations, the underlying transformation mechanisms with respective kinetic factors and hence the impact of polymorphism on pharmaceutical formulations. Keywords: Bioavailability, Crystallization, Polymorphism

Simultaneous Estimation of Lafutidine and Domperidone by Ultraviolet Spectroscopy

A simple, accurate, and precise method for simultaneous estimation of Lafutidine and Domperidone in combined-dosage form have been described. The method employs formation and solving of simultaneous equations using 279 and 284 nm as two analytical wavelengths. This method allows the simultaneous determination of Lafutidine and Domperidone in concentration ranges employed for this purpose with the standard deviation of &lt;1.0% in the assay of tablet.</jats:p

Effective Cancer Theranostics with Polymer Encapsulated Superparamagnetic Nanoparticles: Combined Effects of Magnetic Hyperthermia and Controlled Drug Release

A combination of chemotherapy with nonconventional nanoparticle based physical destruction therapy has been proposed clinically to reduce the prospect of evolution of drug resistance in cancer. Superparamagnetic nanoparticles have been actively used for synergetic cancer therapy including magnetic fluid hyperthermia (MFH) guided by magnetic resonance imaging (MRI). To explore this direction of potential applications in cancer therapy, we have functionalized superparamagnetic La0.7Sr0.3MnO3 nanoparticles (SPMNPs) with an oleic acid-polyethylene glycol (PEG) polymeric micelle (PM) structure, and loaded it with anticancer cancer drug doxorubicin (DOX) in a high loading capacity (∼60.45%) for in vitro delivery into cancer cells. The micellar structure provided good colloidal stability and biocompatibility. Upon drug loading, the cancer cell death rate of 89% was comparable to free DOX (75%) for 24 h, and that the counterstrategy of DOX conjugated SPMNPs-induced hyperthermia resulted the cancer cell extinction up to 80% under in vitro conditions within 30 min. In addition, the preliminary effect of protein corona formation on in vitro drug release and delivery was studied. Finally, in vivo bio distribution of micellar SPMNPs is observed in mice model for 50 mg kg–1 dose of SPMNPs. Taken together, polymeric micelle SPMNPs reported here can serve as a promising candidate for effective multimodal cancer theranostics such as in the combined chemotherapy–hyperthermia cancer therapy

Synthesis of titanium nanoparticles using Allium eriophyllum Boiss aqueous extract by green synthesis method and evaluation of their remedial properties

The application of nanotechnologies to medicine, or nanomedicine, which has already demonstrated its tremendous impact on the pharmaceutical and biotechnology industries, is rapidly becoming a major driving force behind ongoing developments in the antimicrobial and wound healing fields. This study confirms the potential of Allium eriophyllum Boiss aqueous extract for the green synthesis of titanium nanoparticles (TiNPs). Also, we reveal the antioxidant, cytotoxicity, cutaneous wound healing, antifungal and antibacterial properties of TiNPs. These nanoparticles were characterized using Fourier transform infrared (FT-IR) and UV-visible spectroscopies, X-ray diffraction (XRD), transmission electron microscopy (TEM) and field emission scanning electron microscopy (SEM). FT-IR findings suggested molecular interactions of compounds in the plant were the sources of reducing power, reducing titanium ions to TiNPs. In XRD analysis, 22.8 nm was measured for the crystal size of the nanoparticles. SEM and TEM images indicated a uniform spherical morphology and average diameters of 22 nm. 2,2-Diphenyl-1-picrylhydrazyl experiments were conducted to assess the antioxidant activities, which indicated similar antioxidant potentials for TiNPs and butylated hydroxytoluene. In the antimicrobial part of this study, agar diffusion experiments were done to determine the antibacterial and antifungal characteristics. TiNPs had antifungal activities against Candida guilliermondii, C. krusei, C. albicans and C. glabrata and antibacterial potentials against Gram-negative bacteria (Pseudomonas aeruginosa, Salmonella typhimurium and Escherichia coli O157:H7) and Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae and Bacillus subtilis). Also, these nanoparticles did not have any cytotoxicity against human umbilical vein endothelial cells. In in vivo experiments, TiNP ointment significantly decreased (p <= 0.01) wound area, total cells, macrophages, neutrophils and lymphocytes and notably increased (p <= 0.01) wound contracture, vessels, hydroxyproline, hexosamine, hexuronic acid, fibrocytes and fibrocyte/fibroblast ratio in rats. The results of FT-IR, UV, XRD, TEM and SEM analyses confirm that aqueous extract of A. eriophyllum leaves can be used to yield TiNPs with notable antioxidant, antibacterial, antifungal and cutaneous wound healing potentials without any cytotoxicity. Further clinical trials are necessary for confirmation of these remedial properties of TiNPs in humans