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In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time. [ABSTRACT FROM AUTHOR]

In dermatology, ointments are often mixed as part of drug therapy, but mixing often leads to incompatibility. Three combinations of tetracycline ointment (TC-o) and acyclovir cream (ACV-cr) were prepared at a TC-o:ACV-cr ratio of 1:1 using a brand-name ACV-cr and two generic ACV-cr (samples TC-o+ACV-A, TC-o+ACV-B, and TC-o+ACV-C). Microscopic examination revealed separation in TC-o+ACV-C. Viscosity and elasticity measurement indicated that the storage modulus (G′) and loss modulus (G″) of each of the TC-o+ACV-cr mixtures behaved similarly to those of an ACV-cr and the loss tangent (tan δ) behaved similarly to that of a TC ointment. In addition, differences in the storage modulus (G′) and loss modulus (G″) of the TC-o+ACV-cr mixtures were noted. To assess stability, each TC-o+ACV-cr mixture was stored away from direct sunlight at 25°C and an RH of 84% and at 4°C (in a refrigerator). HPLC revealed that the ACV content in each TC-o+ACV-cr mixture remained at 95–105% for up to 14 days under both sets of storage conditions. A decline in TC content in each TC-o+ACV-cr mixture was not noted with storage at 4°C but was noted over time with storage at 25°C and an RH of 84%. In addition, significant differences in the percent decline in TC content in each TC-o+ACV-cr mixture occurred with storage at 25°C and an RH of 84%. Thus, differences in physical properties and stability may occur when combining brand-name and generic drugs, and temperature and humidity may be the cause of the TC-o's incompatibility. [ABSTRACT FROM AUTHOR]

Abstract: Current definitions of lotions, gels, creams and ointments vary depending on literature source, market history or traditional use. This often leads to confusion when deciding which dosage form to prescribe and/or purchase. The existing classification of topical dosage forms needs to be re-examined to ensure that definitions for different dosage forms are based on consistent scientific principles and that dosage forms can be distinguished from one another. The purpose of this study is to obtain a scientifically based, systematic classification of dosage forms for topical drugs. A variety of prescription and over-the-counter topical products currently marketed as lotions, gels, creams, and ointments are evaluated using different techniques including rheology (viscosity and shear rate versus shear stress), loss on drying (LOD), specific gravity, surface tension, thermogravimetric analysis (TGA), water absorption, dilution properties, microscopic evaluation, transmittance of visible light, appearance and composition. Rheology is the most discriminating property separating creams and lotions. Water plus volatiles (as measured by LOD) and composition separate ointments and creams. Composition and thermal behavior separate gels from the other dosage forms. Based on these findings, new definitions and a decision tree are presented to assist in the determination of the appropriate nomenclature for a topical dosage form. [Copyright &y& Elsevier]

The in vitro release profiles and the bleeding phenomenon of Tacrolimus and propylene carbonate (PC) as a dispersing solvent for Tacrolimus drug substance in Tacrolimus ointment were investigated when changing concentrations of Tacrolimus and PC in the ointment were used, respectively. The bleeding test result indicated that Tacrolimus was in equilibrium between inside and outside of PC droplets in intact ointment base. A cumulative release amount of Tacrolimus from ointment, plotted against the square root of time, showed a straight line initially with a slope of q1 followed to change a slope to be q2 at a certain time, where the relation of these slopes being q1. The q1 values increased with the concentration of Tacrolimus but decreased with PC concentration in Tacrolimus ointment. And the q2 values increased with Tacrolimus concentration but were independent of PC concentration. These profiles indicated that there were two phases for Tacrolimus release from ointment, namely, first phase was related with the period during PC release and the second phase was related with the state of ointment after PC release. When the PC release was applied to the Higuchi’s release equation, the above slope q1 was found to be correlated to the parameter of A/φ0, where A was a parameter of release rate of PC and φ0 was an initial volume fraction of PC droplets. It should be indicated that more rapid release rate of PC rather than that of Tacrolimus resulted in the generation of amorphous phase of Tacrolimus outside of remaining PC droplets. During PC release, the slope q1 could be influenced by the thermodynamic activity of Tacrolimus dissolved in PC droplets. After PC release, it would be reasonable to speculate that the amorphous cluster of Tacrolimus with a constant thermodynamic activity would give constant q2 values regardless of PC contents in Tacrolimus ointment. [Copyright &y& Elsevier]

Excipients from different sources may lead to significant differences in the performance of drug products, posing challenges in product quality control. A previous report showed that the drug release rates from ophthalmic ointments were affected by source variation of white petrolatum. To understand the physicochemical properties including the microstructure of white petrolatum and the impact of this on the performance of finished products, the following were investigated: rheological properties, thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), as well as structural characteristics (polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS)). The rheological parameters may be indicative of the drug release rate of the finished ophthalmic ointments when using a process involving hot-melting with immediate cooling. The white petrolatum from the four different sources also showed different thermal behavior. According to SAXS and WAXS, all of the petrolatum showed semi-crystalline behavior with different extents of crystallinity (from 9.5% to 16.9%). The crystalline domains of the petrolatum are ordered in an orthorhombic structure forming lamellar sheets with a periodicity from 9.1 nm to 9.9 nm. An in-depth understanding of the semi-crystalline structure was obtained and it provided valuable information for formulation optimization and characterization of petrolatum-based products. [ABSTRACT FROM AUTHOR]