Mohammad T. Islam

Rheological characterization of topical carbomer gels neutralized to different pH

AbstractPurpose. The primary objective of this study is to perform detailed and extensive rheological characterization of rheology of carbomer (Carbopol) microgels formulated using a solvent system typically used in topical gel formulations. Solvents like glycerin and propylene glycol can alter rheology and drug delivery characteristics of topical gels owing to their different viscosities and due to the change in solvent-polymer and solvent-solvent interactions. Methods. Aqueous gels with different pH were prepared by dissolving cross-linked Carbopol polymers in a co-solvent system comprising water, propylene glycol, and glycerol and subsequently neutralizing the carboxylic groups of the polymers with triethanolamine (TEA). Oscillatory, steady, and transient shear measurements were performed to measure viscoelastic properties, temperature dependency, yield strength, and thixotropy of carbomer pharmaceutical gels. Results. The topical pharmaceutical gels exhibit remarkable temperature stability. Flow curves obtained at different temperatures indicate Carbopol microgels show much more pseudoplastic behavior (lower power law index) compared to Carbopol gels dissolved only in water. Substantial yield strength is required to break the microgel network of the topical gels. The gel samples exhibit modest thixotropy at higher deformation rates. Conclusions. The rheological behavior of the Carbopol microgels do not change appreciably in the pH range 5.0-8.0, and the gels can be used as effective dermatological base for topical applications.

Molecular heterogeneity analysis of poly(amidoamine) dendrimer-based mono- and multifunctional nanodevices by capillary electrophoresis.

Poly(amidoamine) (PAMAM) dendrimer-based nanodevices are of recent interest in targeted cancer therapy. Characterization of mono- and multifunctional PAMAM-based nanodevices remains a great challenge because of their molecular complexity. In this work, various mono- and multifunctional nanodevices based on PAMAM G5 (generation 5) dendrimer were characterized by UV-Vis spectrometry, (1)H NMR, size exclusion chromatography (SEC), and capillary electrophoresis (CE). CE was extensively utilized to measure the molecular heterogeneity of these PAMAM-based nanodevices. G5-FA (FA denotes folic acid) conjugates (synthesized from amine-terminated G5.NH(2) dendrimer, approach 1) with acetamide and amine termini exhibit bimodal or multi-modal distributions. In contrast, G5-FA and bifunctional G5-FA-MTX (MTX denotes methotrexate) conjugates with hydroxyl termini display a single modal distribution. Multifunctional G5.Ac(n)-FI-FA, G5.Ac(n)-FA-OH-MTX, and G5.Ac(n)-FI-FA-OH-MTX (Ac denotes acetamide; FI denotes fluorescein) nanodevices (synthesized from partially acetylated G5 dendrimer, approach 2) exhibit a monodisperse distribution. It indicates that the molecular distribution of PAMAM conjugates largely depends on the homogeneity of starting materials, the synthetic approaches, and the final functionalization steps. Hydroxylation functionalization of dendrimers masks the dispersity of the final PAMAM nanodevices in both synthetic approaches. The applied CE analysis of mono- and multifunctional PAMAM-based nanodevices provides a powerful tool to evaluate the molecular heterogeneity of complex dendrimer conjugate nanodevices for targeted cancer therapeutics.

Scission-induced bounds on maximum polymer drag reduction in turbulent flow

We report the direct quantification of molar mass degradation in the drag-reducing polymers polyethylene oxide (PEO) and polyacrylamide (PAM) in turbulent pipe flows with an upstream tapered contraction. We find that entrance effects associated with the upstream contraction dominate the polymer degradation. Quantifying degradation according to the scaling relationship γw∝Mws−n, the exponent n is determined to be −2.20±0.21 and −2.73±0.18 for PEO and PAM, respectively. Here Mws is the steady-state (or limiting) weight-average scission molar mass. A methodology is devised to circumvent polymer degradation due to the upstream contraction and thereby conduct degradation experiments in which only the turbulent flow in the pipe is responsible for chain scission. In this case, the scission-scaling relationship for PEO is γw∝Mw−3.20±0.28. Here Mw is the degraded weight-average molar mass after one pass through the 1.63-m length of pipe. Based on these scaling relationships we obtain a new upper limit for polyme...

The Potential of Raman Spectroscopy as a Process Analytical Technique During Formulations of Topical Gels and Emulsions

AbstractPurpose. The primary objective of this study is to investigate the possibility of using Raman spectroscopy as a process analytical technique (PAT) for quality control during manufacturing of topical dosage forms. Methods. A fiber-optic Raman probe was used to monitor the formulation of pharmaceutical gel and emulsion in laboratory scale. Raman shifts of typical commercial raw materials used in topical dosage forms were measured to ascertain the potential of this technique for monitoring and analyzing topical products. Spectra of some well-characterized topical gels manufactured in our laboratory were also measured. Results. Commercial raw materials were found to be Raman sensitive. Due to the difference in chemical composition, raw materials exhibit characteristic peaks that can be exploited to monitor formulation processes. Spectra taken during formulation of an emulsion using Carbopol Ultrez as thickener and Tefose as emulsifying agent show changes in Raman shifts immediately after major formulation steps. Conclusions. The findings from this work suggest that Raman spectroscopy can be a valuable process analytical technique for quality control of topical gel and cream formulations.

Fourier Transform Infrared Spectroscopy for the Analysis of Neutralizer- Carbomer and Surfactant-Carbomer Interactions in Aqueous, Hydroalcoholic, and Anhydrous Gel Formulations

The objective of the present study is to evaluate the polymer-surfactant and polymer-neutralizer interactions in topical aqueous, anhydrous, and hydroalcoholic gel formulations using Fourier transform infrared (FTIR) spectroscopy. The gels were prepared by dispersing Carbomer (Carbopol 980) in water and ethanol for aqueous and anhydrous systems, respectively. Glycerol and propylene glycol were also added to ensure that the compositions of gels closely resembled those used in typical topical gel formulations. Comparisons of the spectra of Carbopol dispersions in aqueous, anhydrous, and hydroalcoholic systems, performed for the first time, show Carbopol-neutralizer and Carbopol-surfactant interactions vary depending on the nature of the solvents used for gel formation. Analysis of the spectra of aqueous gel formulations indicates significant presence of ionized carboxyl groups only at higher pH (∼8.0). Drying of the aqueous gels causes a shift in the carbonyl stretch band toward higher energy, suggesting changes in polymer-neutralizer interaction. Anhydrous gels exhibit 2 different carbonyl stretch bands: the one at ∼1653 cm−1 is related to the carboxyl group that is hydrogen bonded and is akin to hydrous gels; the second one at ∼1717 cm−1 is indicative of free carbonyl groups. The carbonyl bands of dried gels appear at different energy levels than the solvated gels. This shift resulting from solvent evaporation, reported for the first time, indicates changes in hydrogen bond characteristics. The results show that FTIR can be a good technique compared with other more time-consuming means of analysis for topical formulations.

Effect of macromolecular polymer structures on drag reduction in a turbulent channel flow

This paper presents the influence of injected polymer solutions on turbulence in fully developed channel flows. In particular, it investigates the impact of concentration and mixing of the polymer solution on drag reduction. It is observed, via flow visualization and birefringence measurements, that for large injection concentrations macromolecular polymer structures exist in the flow. They are found to be mostly located in the neighborhood of the channel centerline. Laser Doppler velocimetry was used to characterize the mean and turbulent flow with and without the presence of macromolecular polymer structures.