Gas diffusion from an encapsulated microbubble is modeled using an explicit linear relation for gas permeation through the encapsulation. Both the cases of single gas (air) and multiple gases (perfluorocarbon inside the bubble and air dissolved in surrounding liquid) are considered. An analytical expression for the dissolution time for an encapsulated air bubble is obtained; it showed that for small permeability the dissolution time increases linearly with decreasing permeability. A perfluorocarbon-filled contrast microbubble such as Definity was predicted to experience a transient growth due to air infusion before it dissolves in conformity with previous experimental findings. The growth phase occurs only for bubbles with a critical value of initial partial mole fraction of perfluorocarbon relative to air. With empirically obtained property values, the dissolution time of a 2.5 micron diameter (same as that of Definity) lipid coated octafluoropropane bubble with surface tension 25 mN/m predicts a lifetime of 42 minutes in an air saturated medium. The properties such as shell permeability, surface tension, relative mole fraction of octafluoropropane are varied to investigate their effects on the time scales of bubble growth and dissolution including their asymptotic scalings where appropriate. The dissolution dynamics scales with permeability, in that when the time is nondimensioanlized with permeability, curves for different permeabilities collapse on a single curve. Investigation of bubbles filled with other gases (non-octafluoropropane perfluorocarbon and sulfur hexafluoride) indicates longer dissolution time due to lower solubility and lower diffusivity for larger gas molecules. For such micron size encapsulated bubbles, lifetime of hours is possible only at extremely low surface tension (<1mN/m) or at extreme oversaturation.

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Micron-size bubbles encapsulated by a stabilizing layer of surface-active materials are used in medical ultrasound imaging and drug delivery. Their destruction stimulated by ultrasound in vivo plays a critical role in both applications. We investigate the destruction process of microbubbles in a commercially available contrast agent by measuring the attenuation of ultrasound through it. The measurement is performed with single-cycle bursts from an unfocused transducer ͑with a center frequency of 5 MHz͒ for varying pressure amplitudes at 50-, 100-, and 200-Hz pulse repetition frequencies ͑PRF͒ with duty cycles 0.001%, 0.002%, and 0.004%, respectively. At low excitation, the attenuation is found to increase with time. With increased excitation level, the attenuation level decreases with time, indicating destruction of microbubbles. There is a critical pressure amplitude ͑ϳ1.2 MPa͒ for all three PRFs, below which there is no significant bubble destruction. Above the critical pressure amplitudes the rate of destruction depends on excitation levels. But at high-pressure amplitudes the destruction becomes independent of excitation pressure amplitude. The results are interpreted to identify two different mechanisms of bubble destruction by its signature in attenuation, namely, slow dissolution by diffusion and catastrophic shell rupture. The different modes are discussed in detail with their implications in medical applications.

Abstract. A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility, dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer hydroxypropyl methylcellulose (HPMC K 3 LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of HPMC K 3 LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy, and Fourier-transform infrared spectroscopy. In vitro-in vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol and triglyceride levels than the SIM. The lowviscosity grade HPMC acts as a surfactant, which enhances the wetting of drug and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM.

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