A solid dispersion based on milk-micelle as a drug-carrier for the enhancement of the aqueous solubility of ritonavir

The goal of present investigation was to evaluate the feasibility of formulating a solid-dispersion using milk-micelles as drug-carriers, to enhance the aqueous solubility of ritonavir

Drug-Excipient Compatibility Studies in Formulation Development: Current Trends and Techniques

The safety, efficacy, quality and stability of a formulation are the cornerstones of any new drug development process. In order to consistently maintain these attributes in a finished dosage form, it is important to have a comprehensive understanding of the physico-chemical characteristics of the active pharmaceutical ingredient (API), as well as all other components (e.g. excipients, manufacturing aids, packaging materials) of the drug product. In a new drug development process, a detailed characterization of the API and other formulation components is usually carried out during the preformulation stage. The preformulation stage involves characterization of several aspects of the API including solubility, dissolution, permeability, polymorph/salt screening, stability (solidstate and solution-state), ionization properties, particle size distribution, API-excipient compatibilities etc. [1]. Excipients are ubiquitous to virtually every pharmaceutical formulation, and facilitate the manufacture, stability, administration, delivery of the API, and/or provide other functionalities to the dosage form. Excipients are used to improve processing (e.g. improving powder flow [2, 3], powder compactibility [4-6] etc.), enhance aesthetics (e.g. identification, branding etc. [7]), optimize product performance (e.g. modified drug-release [8-11]), and/or to facilitate patient compliance (e.g. taste masking [12-15]). They may constitute anywhere from 1 to 99 % of the total formulation mass. Due to the intimate contact of the API with one or more excipients in a formulation, there exists a likelihood of physical and/or chemical interactions between them. Any such interactions may result in a negative impact on the physical, stability or performance attributes of the drug product [16, 17]. The choice of excipients is of crucial importance to avoid these negative effects, and to facilitate the development of a robust and an effective formulation [18-20]. Thus, for a rational selection of excipients, screening of excipient-API compatibility is recognized as an important aspect of formulation development. Moreover, the USFDA’s 21st century current Good Manufacturing Practices (cGMP) initiative and International Council on Harmonization (ICH) Q8 guidelines encourage the pharmaceutical manufacturers to apply Quality by Design (QbD) principles in their drug development process [21, 22]. These guidelines include expectations of a clear understanding of any interactions between the formulation components. Moreover, recent advances in various thermal and non-thermal analytical techniques have led to an improved efficiency in the detection, monitoring and prevention of the incompatibilities early in the drug development process [23, 24]. This article aims to provide a brief overview of the nature of drug-excipient incompatibilities; as well as current trends and techniques used to evaluate these compatibilities in formulation development

Formulation of a drug-phospholipid complex (Naturosome) to enhance the aqueous solubility of standardized extract of Centella asiastica (SCE)

Purpose: To evaluate the enhancement of aqueous solubility of standardized extract of Centella asiastica, a natural drug with known anti- Alzheimer’s activity, by formulating its complex (Naturosome) with a phospholipid - Phospholipon® 90H

Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties

The enhancement of the aqueous solubility of ritonavir via formulation of a drug-phospholipid complex

Objective: To evaluate the enhancement of aqueous solubility of a poorly water soluble drug ritonavir by forming its complex with a phospholipid (Phospholipon®90H)

Root exudates associated with the resistance of four chickpea cultivars (Cicer arietinum) to two races of Fusarium oxysporum f.sp. ciceris

The germination of race 1 spores of F. o. f.sp. ciceris was significantly inhibited by the root exudate of the wilt-resistant chickpea cultivars CPS1 and WR315 compared with untreated spores and spores treated with root exudates from susceptible cultivars. The effect was concn dependent, such that the exudate from 1 g of root in 2 ml of water almost completely inhibited spore germination, whereas the exudate from 1 g of root in 20 ml of water did not. The inhibitory effects of the active exudates were negated when the apolar components of the exudates were removed by extraction with ethyl acetate. The root exudates of the susceptible cv. JG62 and the late wilting cv. H208 did not inhibit germination. The hyphal growth of germinated spores was also strongly inhibited by the concentrated exudates of CPS1 and WR315, and diluted exudates were less potent. The highest concn of the exudate of the susceptible cv. JG62 showed some inhibition of hyphal growth, whereas none of the exudates of H208 contained any antifungal activity. The effect of the exudates on the spores of race 2 was similar to that reported for race 1, except that the water-soluble components of the crude root exudate of WR315 after ethyl acetate extraction also significantly inhibited germination. Overall, the spores of race 2 appeared to be more susceptible to the effects of the exudates. The ethyl acetate fractions of the root exudates of CPS1 and WR315 strongly inhibited germination and hyphal growth of both race 1 and race 2, the effect being concn dependent. It is concluded that the resistance of chickpeas to vascular wilt depends, at least in part, on antifungal activity of root exudates. Differences in the expression of resistance in the field could depend upon the concn or rate of production of constitutive antifungal components by the root

Physical properties and solubility studies of Nifedipine-PEG 1450/HPMCAS-HF solid dispersions

Low-order high-energy nifedipine (NIF) solid dispersions (SDs) were generated by melt solvent amorphization with polyethylene glycol (PEG) 1450 and hypromellose acetate succinate (HPMCAS-HF) to increase NIF solubility while achieving acceptable physical stability. HPMCAS-HF was used as a crystallization inhibitor. Individual formulation components, their physical mixtures (PMs), and SDs were characterized by differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). NIF solubility and percent crystallinity (PC) were determined at the initial time and after 5 days stored at 25 °C and 60% RH. FTIR indicated that hydrogen bonding was involved with the amorphization process. FTIR showed that NIF:HPMCAS-HF intermolecular interactions were weaker than NIF:PEG 1450 interactions. NIF:PEG 1450 SD solubilities were significantly higher than their PM counterparts (p \u3c 0.0001). The solubilities of NIF:PEG 1450:HPMCAS-HF SDs were significantly higher than their corresponding NIF:PEG 1450 SDs (p \u3c 0.0001-0.043). All the SD solubilities showed a statistically significant decrease (p \u3c 0.0001) after storage for 5 days. SDs PC were statistically lower than their comparable PMs (p \u3c 0.0001). The PCs of SDs with HPMCAS-HF were significantly lower than SDs not containing only PEG 1450. All SDs exhibited a significant increase in PC (p \u3c 0.0001–0.0089) on storage. Thermogravimetric analysis results showed that HPMCAS-HF bound water at higher temperatures than PEG 1450 (p \u3c 0.0001–0.0039). HPMCAS-HF slowed the crystallization process of SDs, although it did not completely inhibit NIF crystal growth

Legumes Pathology (Chickpea): Report of work June 1989-July 1990

At ICRISAT Center, Patancheru, large number of chickpea breeding mataria1s and several nurseries were screened in wilt sick plots. The material was planted in 4-meter rows, 60 cm apart. Susceptible check JG 62 which was planted after every two test rows, showed 100% mortality within a month after sowing..

Seed transmission of Fusarium udum in pigeonpea and its control by seed-treatment fungicides

F. udum was transmitted by infected seeds of 5 wilt susceptible pigeonpea cultivars collected from diseased susceptible pigeonpea cultivars collected from diseased plants. The fungus was not isolated from the wilt susceptible cultivars ICP 2376 and ICP 8518. Seed treatment with a mixture of benomyl and thiram completely eradicated the pathogen., 7 ref., F. udum was transmitted by infected seeds of 5 wilt susceptible pigeonpea cultivars collected from diseased susceptible pigeonpea cultivars collected from diseased plants. The fungus was not isolated from the wilt susceptible cultivars ICP 2376 and ICP 8518. Seed treatment with a mixture of benomyl and thiram completely eradicated the pathogen