Drug In Powder Form Research Articles

Abstract 824: Statistical optimization of stable Quercetin nanoparticles for tumor targeting

Abstract Quercetin is a well-known flavonoid with a significant in vitro anticancer effect and low toxicity profile. Despite of that, its clinical use is still limited because of its low solubility, bioavailability, and instability in physiological conditions. The aim of this study was to develop and optimize stable quercetin nanoparticles targeting tumor cells within the body. Quercetin nanoparticles were synthesized using solvent emulsification technique using zein, beta-cyclodextrin, and pectin at different concentrations. The prepared formulations were optimized using factorial response surface analysis. The stability of the optimized quercetin nanoparticles in conditioned media, obtained from subculture of colorectal cancer cell line HCT-116, was compared to the stability of the free drug powder over 24 h. Moreover, the cytotoxic effect of Quercetin powder and the optimized Quercetin nanoparticles were evaluated against two colorectal cancer lines (HT-29, and HCT116), using MTT assay, under normoxic conditions. Annexin-V/FITC apoptotic assay was used to detect the number of cells that underwent apoptosis using flow cytometry. The optimized formulation was composed of 10 mg of zein and 31.35 mg beta-cyclodextrin, with no pectin. It had particle size of 221 nm, polydispersity index of 0.115, zetapotential of 7.65 mV. The stability of the optimized quercetin nanoparticles in the conditioned media of HCT-116 was significantly higher than the free drug powder over 24 h. In HT-29, the optimized nanoparticles and the free drug had IC50 of 29.33 µM and 60.78 µM, respectively. In HCT-116, optimized nanoparticle and the free drug had IC50’s 31.11 µM and 59.20 µM, respectively. The flow cytometric analysis after annexin-V/FITC staining showed that treatment with the optimized quercetin nanoparticles significantly induced total apoptosis in the two colorectal cancer lines (HT-29 and HCT 116) when compared to the free drug and plain nanoparticles. In conclusion, the optimized quercetin nanoparticles were found to be capable of increasing drug stability in physiological fluids as well as increasing its cytotoxic effect in two colorectal cancer cell lines by apoptosis induction when compared to the drug in powder form as well as plain nanoparticles. Citation Format: Nourhan Khaled Hassan, Eman El-labbad, Jayalakshmi jagal, Mohamed Haider, Ibrahim El-sayed. Statistical optimization of stable Quercetin nanoparticles for tumor targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 824.

Preparation and Characterization of Poly(vinyl acetate-co-2-hydroxyethyl methacrylate) and In Vitro Application as Contact Lens for Acyclovir Delivery.

A series of poly(vinyl acetate-co-2-hydroxyethylmethacrylate)/acyclovir drug carrier systems (HEMAVAC) containing different acyclovir contents was prepared through bulk free radical polymerization of 2-hydroxyethyl methacrylate with vinyl acetate (VAc) in presence of acyclovir (ACVR) as the drug using a LED lamp in presence of camphorquinone as the photoinitiator. The structure of the drug carrier system was confirmed by FTIR and 1HNMR analysis, and the uniform dispersion of the drug particles in the carrier was proved by DSC and XRD analysis. The study of the physico-chemical properties of the prepared materials, such as the transparency, swelling capacity, wettability and optical refraction, was carried out by UV-visible analysis, a swelling test and measurement of the contact angle and the refractive index, respectively. The elastic modulus and the yield strength of the wet prepared materials were examined by dynamic mechanical analysis. The cytotoxicity of the prepared materials and cell adhesion on these systems were studied by LDH assay and the MTT test, respectively. The results obtained were comparable to those of standard lenses with a transparency of 76.90-89.51%, a swelling capacity of 42.23-81.80% by weight, a wettability of 75.95-89.04°, a refractive index of 1.4301-1.4526 and a modulus of elasticity of 0.67-1.50 MPa, depending on the ACVR content. It was also shown that these materials exhibit no significant cytotoxicity; on the other hand, they show significant cell adhesion. The in vitro dynamic release of ACVR in water revealed that the HEMAVAC drug carrier can consistently deliver uniformly adequate amounts of ACVR (5.04-36 wt%) over a long period (7 days) in two steps. It was also found that the solubility of ACVR obtained from the release process was improved by 1.4 times that obtained by direct solubility of the drug in powder form at the same temperature.

Development and evaluation of methotrexate nanocomposites using Β-cyclodextrins/alginate polymers and response surface methodology

β-cyclodextrin and alginate polymers have been extensively investigated for their use in drug delivery systems. β-Cyclodextrin-alginate nanoparticles (CD/Alg) as an innovative drug carrier was the preapared by ionic chelation method. Methotrexate (MTX) as model drug was loaded onto the β-CD/Alg nanoparticles to form MTX-CD/Alg nanocomposites, via ionic interactions. The study was to investigate the changes in independent variables (concentration of CD, Alg and CaCl2) loading efficiency and particle size using 4-levels of CD, 5-levels of Alg and 4-levels of CaCl2. The Optimum nanocomposite has %LE (58.1% and particle size (213 nm). The prepared nanocomposites were chrecterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), a thermogravimetric analysis (TGA) and a release study. FTIR analysis displayed the drug into nanocomposites. The XRD pattern of MTX-β-CD/Ag nanocomposite suggested a peak at 2θ = 44.6° with the amorphous properties. A novel MTX-CD/Alg nanocomposites was developed. Optimized, characterized, and release studied was performed. These nanocomposites will be prmosing by delivering the drug in powder form

Enhancement of Physico-chemical and Biological Activities of Antibiotic Cephradine by Gamma Irradiation

Radiation based sterilization is a common tool for microbial inactivation in different products on a commercial scale. The objective of the current study was to determine the effect of gamma radiation on cephradine antibiotic in the solid-state to enhance its biological response. Cephradine drug in powder form was treated with different doses (25, 50, 75, 100 and 125 kGy) of the cobalt-60 source in a Gamma cell-220 at a current rate of 8.5 gray/h. The effect of radiation doses on antibiotic was assessed with the help of different analytical techniques such as FT-IR, UV, XRD, SEM and HPLC. The UV spectra of radiated cephradine show some changes in the absorption peak by increasing the intensity of radiations while only slight changes were observed in the other peaks. The crystallinity of antibiotics was tested by the XRD and SEM, it shows a little morphological change. The FT-IR data disclosed significant changes in the absorption bands. The HPLC analysis showed reports an insignificant change which revealed that the radiolytic products are not formed. The radiated cephradine exposes a remarkable antibacterial activity against bacteria; indicating the enhancement of a biological response. In summary, a slight change was observed in cephradine drug with the radiation but the drug was chemically stable.
 

Clinical evaluation of Tukhm-e-Sambhalu (Vitex negundo Linn. seed) in Usr-e-Tams Ibtedayee (primary dysmenorrhoea)

Primary dysmenorrhoea is painful menstrual cramps of uterine origin during menstruation without any identifiable pathological lesion. It is commonly seen in menstruating and lasting 12-24 h. Its prevalence is wide, as more than 70% of teenagers and 30-50% of menstruating women suffer from varying degree of discomfort. Tibbe-e-Unani claims to possess safe and effective therapeutic substances which are commonly prescribed in the management of primary dysmenorrhoea (Usr-e-Tams Ibtedayee), but despite being used in the treatment successfully, most of them have yet not been studied scientifically. Therefore, an attempt has been made in the present study to evaluate a single Unani drug Tukhm-e-Sambhalu (Vitex negundo) on 30 patients for its efficacy in primary dysmenorrhoea. The patients were administered test drug in powder form (5 g), by oral rout, twice a day for 7 days, starting 2 days before the onset of menstruation up to 5th day of menses, for three consecutive cycles. The important clinical features like pain in suprapubic region, pain in thigh, backache and headache were significantly reduced in patients treated with test drug. Thus, findings of this study suggested that Tukhm-e-Sambhalu is safe and effective in ameliorating the disease primary dysmenorrhoea.

Development of standardization parameters of crude drugs used in Ayurvedic Balarista formulation

‘Balarista’ is an important Ayurvedic arista formulation containing twelve crude drugs among which Sida cordifolia and Withania somnifera are the two major drugs. The Ayurvedic Formulary of India mentions various usages of Balarista, but it is mainly used in the treatment of rheumatoid arthritis. This study deals with the evaluation of pharmacognostic and physico-chemical properties of all incorporated drugs along with the HPLC and GC–MS analysis of the two main drugs. The macroscopic, microscopic, powder microscopy and physico-chemical parameters of different drugs were assessed according to the Ayurvedic Pharmacopoea of India. The scanning electron microscopic study, fluorescence analysis and powder behavior studies of various drugs in powder form were also carried out. The quantification of vasicine and total withanolides were analyzed in chloroform extract of Sida cordifolia and Withania somnifera root by HPLC method. Further, presences of other phytoconstituents were also confirmed by GC–MS analysis. The macroscopical, organoleptic, histological, powder characteristics and scanning electron microscopic images of various drugs revealed the important diagnostic features. The physico-chemical, fluorescence analysis and powder behavior characteristics provided useful tools to differentiate them from the adulterants. The HPLC analysis detected percentage of vasicine and total withanolide (withanoside IV, withanoside V, withaferin A, 12-Deoxy withastramonolide, withanolide A and withanolide B) in Sida cordifolia and Withania somnifera root respectively. GC–MS analysis identified fifty bioactive compounds in both the drugs. The pharmacognostical, physico-chemical and chromatographic assessment of these medicinally important plant drugs could be helpful for their authentication and in ensuring the quality of Balarista formulation.

Effect of Incorporation of Antifungal Agents on the Ultimate Tensile Strength of Temporary Soft Denture Liners.

To investigate the ultimate tensile strength of temporary soft denture liners modified by minimum inhibitory concentrations (MICs) of antifungal agents for Candida albicans biofilm (SC5314) determined in previous microbiological research. Dumbbell-shaped specimens (n = 7) with a central cross-sectional area of 6 × 3 × 33 mm were produced by Softone and Trusoft, without (control) or with incorporation of drugs in powder form at MICs for C. albicans biofilm (per g of material powder): nystatin (0.032 g), chlorhexidine diacetate (0.064 g), ketoconazole (0.128 g), miconazole (0.256 g), and itraconazole (0.256 g). After plasticization, specimens were immersed in distilled water at 37°C for 24 hours, 7 or 14 days, and then tested in tension in a universal testing machine at 40 mm/min. Data of tensile strength (MPa) and elongation percentage (%) were submitted to 3-way ANOVA and Tukey's test (α = 0.05). At the end of 14 days, the tensile strength for both materials was significantly lower in the groups modified by miconazole and itraconazole compared to the other groups (p < 0.0001), which showed no significant difference between them (p > 0.05). After 7 and 14 days in water, miconazole and itraconazole added into both materials resulted in significantly lower elongation percentages compared to the other antifungal agents and control (p < 0.0001), which were similar to each other (p > 0.05). The addition of the nystatin, chlorhexidine, and ketoconazole at MICs for C. albicans biofilm resulted in no harmful effects on the tensile strength and elongation percentage of the temporary soft denture liner materials up to 14 days.

Pharmacognostical and Phytochemical Studies of Helleborus niger L Root.

Background:Helleborus niger L (Ranunculaceae) is used Ayurvedic and Unani systems and other herbal medicine systems. The roots of H. niger have a good medicinal value.Aims:To conduct a pharmacognostical and phytochemical study of H. niger.Materials and Methods:The pharmacognostical studies on roots including parameters such as taxonomical, macroscopic, microscopic characters, physico-chemical, ultra-violet analysis and phytochemical studies are established.Results:Macroscopically, the roots are brownish-black in colour, cylindrical in shape, feeble odour, slightly acrid taste with irregularly branched. Microscopically the root showed the presence of epidermis, air-chambers, fissure periderm, periderm, inner cortex, pith, phloem, xylem, vessels and xylem vessels. Microscopic examination of the powder showed the presence of parenchyma cells, parenchyma mass, periderm, cell inclusion, laticifer, lateral wall pith, perforation, xylem bundle and xylem elements. Ultra-violet and ordinary light analyses with different reagents were conducted to identify the drug in powder form. Physico-chemical evaluation established, Ash values - Total, acid insoluble, water soluble and sulphated ash values were 7.3%, 4.1%, 3.7% and 5.2%, respectively. Extractive values - Alcohol soluble, water soluble and ether soluble extractive values were 22.8%, 7.4% and 5.6%, respectively. Loss on drying was 3.3%. Preliminary phytochemical screening showed the presence of carbohydrate, glycoside, saponins, flavonoid, phytosterols, tannins and phenolic compounds.Conclusions:The results of the study can serve as a valuable resource of pharmacognostic and phytochemical information. This will serve as appropriate, standards for discovery of this plant material in future investigations and applications and also contribute towards establishing pharmacopoeial standards.

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles

Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery.

Analysis of the Loss Amounts of Hygroscopic Drug in Powder form in Dispensing, Storage and Process Improvement to Decrease Loss

Analysis of the Loss Amounts of Hygroscopic Drug in Powder form in Dispensing, Storage and Process Improvement to Decrease Loss

Double‐blind comparison between beclomethasone dipropionate as aerosol and as powder in patients with nasal polyposis

Beclomethasone dipropionate as a pressurized aerosol is effective in nasal polyposis, but the efficacy is only moderate. In these partly-blocked noses, it seems possible that the insufflated drug in powder form is better distributed over the mucous membrane than the pressurized aerosol. To test this hypothesis, we treated forty-two patients with nasal polyposis with intranasal beclomethasone dipropionate as a powder and as a pressurized aerosol in a double-dummy, cross-over design. There was no difference between the treatments in sixteen patients, while in twelve cases there was a preference for beclomethasone dipropionate as aerosol, and in fourteen, for the powder form. Fourteen found the aerosol most irritating and nineteen, the powder. Thus, in a group of polyp patients there were no significant differences between the two application forms, but possibly there is a need for both aerosol and powder, as there appeared to be differences in the individual responsiveness to the two types of intranasal medication. Blind microscopy of wiped nasal-smears before and after beclomethasone dipropionate treatment showed a reduction of basophilic cells, and counting of sneezes after medication demonstrated a reduction in the number of sneezes. These results suggest that a reduction of epithelial mediator-cells and of irritant receptor-sensitivity are of importance for the efficacy of topical steroids in rhinitis.

Systematic identification of unknown drugs in powder form by means of ultraviolet spectrophotometry in forensic toxicology.

Systematic identification of unknown drugs in powder form by means of ultraviolet spectrophotometry in forensic toxicology.