Investigation of water vapour sorption mechanism of starch-based pharmaceutical excipients

Starch-based excipients are commonly used in oral solid dosage forms. The effect of particle size and pregelatinisation level of starch-based excipients on their water absorption behaviour have been evaluated. The results showed that starch-based excipients have type ii isotherms, indicating that the principal mechanism of sorption is the formation of monolayer coverage and multilayer water molecules (10–80 RH %). It was found that the particle size of starch-based excipients did not have any influence on the rate of water sorption, whereas the level of pregelatinisation changed the kinetics of water sorption-desorption. Results showed that the higher the degree of pregelatinisation, the higher the rate of water absorption, which is irrespective of particle size. SEM images showed that a partially gelatinised starch had a firm granular structure with small pores and channels on the surface while a fully gelatinised starch had more irregular and spongy like surface with a degree of fractured particles

Synthesis and characterization of a novel chemically designed (Globo)3–DTPA–KLH antigen

In recent years, many experiments have been conducted for the production and evaluation of anticancer glycoconjugated vaccines in developed countries and many achievements have been accomplished with Globo H derivatives. In the current experiment, a new chemically designed triplicate version of (Globo H)3–diethylenetriamine pentaacetic acid (DTPA)–KLH antigen was synthesized and characterized. Immunization with (Globo H)3-DTPA-KLH, a hexasaccharide that is a member of a family of antigenic carbohydrates that are highly expressed in various types of cancers conjugated with DTPA and KLH protein, induced a high level of antibody titer along with an elevated level of IL-4 in mice. Treatment of tumors with the collected sera from immunized mice decreased the tumor size in nude mice as well. None of the immunized mice illustrated any sign of tumor growth after injection of MCF-7 cells compared to the control animals. These findings, based on the newly presented structure of the Globo H antigen, lend exciting and promising evidence for clinical advancement in the development of a therapeutic vaccine in the future

Fundamental study of interactions between water and modified starch products for inclusion in moisture management of solid oral dosage forms

Starch I 500® (ST 1500) is the product of the physical modification of native corn starch (NCS). It is one of the widely used excipients in pharmaceutical formulations, particularly oral dosage forms. As ST 1500 is mainly used as a diluent in oral solid dosage forms, it makes up the bulk of the formulations (probably the highest concentration compared to other excipients such as binder disintegrants and lubricants). Therefore, understanding the water inclusion effect with ST 1500 to scavenge the moisture (water)-sensitive drugs is essential. The states of water associated with ST1500 and the water inclusion effect were investigated extensively. Comprehension of the interaction between moisture and ST 1500 or starched-based excipients allows formulation scientists to design better formulations. The data obtained from DYS suggest that water interacts with ST1500 either by the formation of a monolayer, multilayer coverage, or bulk absorption. DYS analysis revealed that type II (sigmoidal (S) shape isotherm) is the characteristic feature of starch­-based products, showing hysteresis. The appearance of hysteresis reveals that desorption is irreversible, indicating that some water molecules are entrapped within the physical structure. Bulk diffusion was found to be the predominant mechanism of water sorption in starch-based excipients, irrespective of the degree of pregelatinization. The kinetics of the water sorption-desorption is governed by the particle size and the pregelatinization degree. By increasing the particle size, the rate of sorption-desorption decreases. According to DSC and TO analysis, it was confinned that water exists either as free or bound water. Non-freezable water (hydration water) only gets removed at high temperatures before the physical structure of the starch molecules collapse (310-314 °C). The BET model data fit represents no significant change in the concentration of monolayer formation after aw of ~0.34. Multilayer coverage exponentially increases over the range of aw, and the gap indicating hysteresis is seen for the internally absorbed water. All starch-based excipients follow a similar trend, irrespective of the degree of pregelatinization. The specific surface area (SSA) was reduced by increasing the particle size (237.17 m2/g, 233.89 m2/g, and 228.14 m2/g for ST1500 125 µm respectively). Similarly, as the particle size of ST1500 increases, the amount of monolayer formation increases. Unlike NCS, the SSA of ST1500 and LPGS increase by elevating the temperature from 25°C to 50°C. In addition, increasing the temperature from 50°C to 70°C reduces the surface area of ST 1500 and LPGS. There was a significant difference in preserving ASA when 11 %RH compared with 44%RH and 86%RH. However, the difference was not significant for 44%RH and 86%RH moisture-scavenging power due to chemical hydrolysis. NCS was physically modified to investigate the effect of drug release with and without the addition of PYPK30 (as a binder), moisture scavenging power, and lubricant sensitivity of the formulations to magnesium stearate (as a lubricant). The principal mechanism of disintegrating the Mod. NCS was found to be via the volcanic effect that releases the drug in the dissolution media. It was shown that understanding the interaction of moisture with starch-based excipients makes it possible to design multi-functional starch-based excipients with better performance than the original excipient NCS

Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system

Eugenol is the main constituent of clove oil with anti-inflammatory properties. In this work, for the first time, O/W nanoemulsion of eugenol was designed for the evaluation of anti-inflammatory effects as a topical delivery system. Topical formulations containing 1%, 2% and 4% of eugenol as well as a nanoemulsion system containing 4% eugenol and 0.5% piroxicam were prepared. Further to physicochemical examinations, such as determination of particle size, polydispersity index, zeta potential and physical stability, anti-inflammatory activity was examined in carrageenan-induced paw edema in rats. The optimum formulation was found to contain 2% eugenol (oil phase), 14% Tween 20 (surfactant) and 14% isopropyl alcohol (co-surfactant) in water. Nanoemulsion with polydispersity index of 0.3 and median droplet diameter of 24.4 nm (d50) was obtained. Animal studies revealed that the nanoemulsions exhibited significantly improved anti-inflammatory activity after 1.5 h, compared with marketed piroxicam gel. Additionally, it was shown that increasing the concentration of eugenol did not show higher inhibition of inflammation. Also, the nanoemulsion having piroxicam showed less anti-inflammatory properties compared with the nanoemulsion without piroxicam

Pulmonary delivery of rifampicin microspheres using lower generation polyamidoamine dendrimers as a carrier

Different generations (G1, G2 and G3) of polyamidoamine dendrimers (PAMAM) were synthesized and co-spray dried with rifampicin to produce inhalable microspheric particles for pulmonary delivery. The particle size distribution, morphology and density of the designed formulations were characterized by laser diffraction, scanning electron microscopy (SEM) and helium densitometer, respectively. The aerosolization performance of these formulations was investigated using an Andersen cascade impactor. The formulations were efficient aerosols having favorable fine particle fraction (FPF) and emitted fraction (EF), suggesting that the powders were suitable for inhalation. The absorptions of rifampicin following pulmonary administration of different formulations were also examined using an in situ pulmonary absorption method. The pharmacokinetic profiles of different rifampin formulations were studied following intrapulmonary administrations for 60 h. The pharmacokinetics parameters such as Cmax, tmax, t1/2, mean residence time (MRT) and the AUC were calculated separately. It was evident that the tmax value of the formulations was decreased while Cmax value was increased followed by PAMAM dendritic generations increased from G1 to G3. The lower generation PAMAM microspheres were found to have significant impact on the pharmacokinetics parameters of rifampicin and ultimately drug bioavailability. In this study, PAMAM G3 dendritic microsphere was identified as suitable drug carriers for the pulmonary delivery of rifampicin into lung tissues