In-vitro release

By choosing the excipient type and concentration, and by varying the spray-drying parameters, control was achieved over the physical properties of the dry chitosan powders. The in vitro release of betamethasone showed a dose-dependent burst followed by a slower release phase that was proportional to the drug concentration in the range 14-44% w/w [200]. 

In vitro release profiles on phase II and phase III clinical supplies prepared more than 2 years apart are shown in Fig. 2. SeveT al thousand doses were prepared for the phase III trial initiated in 1988. Figure 3 shows the reproducibility of six individual batches of microspheres produced by the solvent evaporation method. Other studies have been reported with similar processes (47). 

FIGURE 2 Comparison of in vitro release profiles of phase II and phase III clinical batches of 90-day norethisterone microspheres. 

FIGURE 3 Batch-to-batch reproducibility of 90-day norethisterone microspheres as determined by in vitro release profiles. 

The in vitro release profiles of many microsphere formulations including steroids can be determined by an ethanol/water model (74). By adjusting the ethanol/water ratio in the receiving fluid, the rate and duration of release can be optimized to afford a rapid evaluation tool for developmental and quality control purposes. The model is not intended to have one-to-one correlation with in vivo results. 

Strobel et al. (101) reported a unique approach to delivery of anticancer agents from lactide/glycolide polymers. The concept is based on the combination of misonidazole or adriamycin-releasing devices with radiation therapy or hyperthermia. Prototype devices consisted of orthodontic wire or sutures dip-coated with drug and polymeric excipient. The device was designed to be inserted through a catheter directly into a brain tumor. In vitro release studies showed the expected first-order release kinetics on the monolithic devices. 

FIGURE 5 Release of [ HJBCNU from compression-molded discs of PCPP-SA, 20 80. Disks 3 mm in diameter and 1 mm thick containing 2.5% [3h]BCNU were prepared by compression molding using either the trituration or solution methods described in the text. In vitro release of ( H]BCNU was measured as described in the text. 

In an extension of this work, pellets of a blend of PCL and hy-droxypropylcellulose containing fluridone were prepared by grinding, blending, and then melt-spinning the mixture with a Berstorff twin screw extruder (78). The extruded rod was subsequently water-quenched and pelletized. Pellets were also prepared by coating bundles of extruded rods with the water-soluble excipients PEG 3350 and PEG 600 (95 5). In vitro release rate measurements were conducted in the simulant medium of 50% aqueous ethanol or hardened water. 

D., Microencapsulation of nitrofurantoin in poly( e-caprolactone) Tableting and in vitro release studies, Int. J. Pharm.. 35. 145-156, 1987. 

Although it was possible to achieve constant in vitro release of levonorgestrel for up to 410 days at which point the experiment was discontinued, release of the drug was not controlled by surface erosion of the polymer but instead the device underwent bulk erosion and release of levonorgestrel was completely controlled by its rate of dissolution. Bulk erosion of the rod-shaped device was evident by scanning electron microscopy as shown in Fig. 17. 

Drug delivery problems associated with pilocarpine, most notably low ocular bioavailability and short duration of action, continue to be significant (44). In an effort to prolong delivery and to avoid undesirable effects, an investigation was carried out on the incorporation and in vitro release of pilocarpine from a soluble film... 

In a series of papers, Gupta et al. (109-112) studied the in vitro release properties of heat-stabilized BSA microspheres containing adriamycin. The biphasic release of drug was attributed to its location in the microsphere. The initial release results from surface desorption and diffusion through pores, while the later release arises from drug within the microsphere, which becomes available as the microsphere hydrates. 

KRISHNAIAH Y S, SEETHA DEVI A, NAGESWARA RAO L, BHASKAR REDDY P R, KARTHIKEYAN R S, SATYANARAYANA V (2001) Guat gum as a carrier for colon specific delivery influence of metronidazole and tinidazole on in vitro release of albendazole from guar gum matrix tablets. J Pharm Pharm Sci. 4 235-43. 

Jordana, M., Richards, C., Irving, L.B. and Gauldie, J. (1988). Spontaneous in vitro release of alveolar macrophage cytokines after the intratracheal instillation of bleomycininrats. Am. Rev. Resp. Dis. 137, 1135-1140. 

High Performance Liquid Chromatographic (HPLC) Analysis. A Waters HPLC system (two Waters 501 pumps, automated gradient controller, 712 WISP, and 745 Data module) with a Shimadzu RF-535 fluorescence detector or a Waters 484 UV detector, and a 0.5 pm filter and a Rainin 30 x 4.6 mm Spheri-5 RP-18 guard column followed by a Waters 30 x 3.9 cm (10 pm particle size) p-Bondapak C18 column was used. The mobile phase consisted of a 45% aqueous solution (composed of 0.25% triethylamine, 0.9% phosphoric acid, and 0.01% sodium octyl sulfate) and 55% methanol for prazosin analysis or 40% aqueous solution and 60% methanol for naltrexone. The flow rate was 1.0 mL/min. Prazosin was measured by a fluorescence detector at 384 nm after excitation at 340 nm (8) and in vitro release samples of naltrexone were analyzed by UV detection at 254 nm. 

Figure 7. In Vitro Release Profile of PHPG-Prazosin Conjugate (Loading 23.9%w/w).

The in vitro degradation profiles of several TDI poly(phosphoester-ure thanes) are shown in Figure 2. It is not possible from this study to correlate the decomposition kinetics with the chemical structure, except for the fact that biodegradability is demonstrated. The in vitro release of 5-FU from PPU-7 is shown in Figure 3. After an initial burst, a reasonably steady and sustained release followed. The UV spectrum of the released 5-FU was identical to that of pure 5-FU, suggesting the chemical integrity of the drug. 

In vitro release of methotrexate from the LDI based films is shown in Figure 7. The release was fast since the drug was imbedded in a thin film, in the order of 50 to 100 microns. The release profile was typical of one seen in diffusion controlled systems. The scattering of the release data was again reminiscent of the mass loss results, and the cause of that is not certain at this point... 

In vitro Release of Desmopressin and Lysine Vasopressin. The release experiments were carried out in triplicate according to the USP paddle method (100 rpm, 37 C, 500 mL water). Appropriate amounts of the cubic phase (typically 100 mg) were weighed in small cups (depth=2 mm, diameter=8 mm) drilled non-... 

Figure 3. In vitro release experiments for dDAVP and LVP in various cubic phases at 37 C. The compositions of the samples are listed in Table n.

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