Not Your Mother's Talcum Powder: Drug Interactions with Old and New Silicates

After outlining the results of extensive studies on drug-silicate interactions, Robin H. Bogner, PhD, concluded, "We're just scratching the surface." She might have added, "pardon the pun": the effect of silicates' heterogeneous surface chemistry is one of the points of study.

During the Wednesday sunrise session at the AAPS Annual Meeting, Bogner and Isabelle Lagadic, PhD, both from the University of Connecticut, educated the audience about old and new silicates. Bogner explained how traditional silicates increase drug dissolution rates, and Lagadic shared study results on engineered silicates for controlled-release drugs.

Bogner reviewed studies conducted over the past two decades on the interaction of drugs and amorphous silicates, which were combined using solvent deposition, co-grinding, spray-drying, melt adsorption, blending, and reduced pressure. All the studies but one showed an increase in the drug dissolution rate. Reviewing her own recent work co-grinding indomethacin and the silicate Neusilin (magnesium aluminometasilicate) in various ratios, Bogner reported that all combinations increased drug amorphization and dissolution rates. Various drug - silicate ratios showed significant differences in stability profiles, however; and in some ratios the amorphized drug reverted to crystalline form over time.

Lagadic's studies have focused on loading drug into engineered silicates to deliver poorly water-soluble drugs. Through different chemical pathways, she developed a functionalized amorphous silicate and a functionalized, ordered mesoporous silicate, which was formed into a tube-like structure using a surfactant template. Both silicates had inorganic functionality on one side and organic functionality on the other.

Lagadic conducted studies loading ibuprofen and naproxen into a hexagonal mesoporous silicate (HMS) and an amino-functionalized HMS (HMS - NH2). For both silicate forms, the drugs were loaded by means of impregnation without co-grinding. Drug was loaded into the HMS using hydrogen bonding between the -OH group of the silicate and the HOOC- group (carboxylic acid) of the drug. Drug was loaded into the HMS - NH2 by means of hydrogen bonding as well as proton transfer between the drug's carboxylic acid and the silicate's amino group, which resulted in NH3+ - -OOC electrostatic interactions.

The results showed promise for the using these silicates in extended-release formulations. Drug release from both silicates was slow, and slower from the HMS - NH2 than from the HMS for both drugs. Naproxen release from HMS - NH2 took between 30 h and 6 d. For both drugs and both silicates, drug release was complete.

In addition, drug release in simulated gastric fluid (pH ~1 - 1.2) was very low compared with drug release in simulated body fluid (pH ~7). This result suggests that these modified silicates could protect drug during its passage through the stomach to allow colon-targeted delivery.

In her future work, Lagadic plans to move from the chemistry laboratory to the pharmaceutical laboratory, where she will investigate silicate matrix dissolution rates in simulated gastric and body fluid and evaluate the toxicity of the drug carriers.

The participants in this session were:
Moderator: Robin H. Bogner, PhD, University of Connecticut

Drug Interactions with Pharmaceutical Silicates, Robin H. Bogner, PhD

Engineering Silicates for Modified Release, Isabelle Lagadic, PhD, University of Connecticut