New Trends in Polymers - Progress in Organic and Physical Chemistry: Structures and Mechanisms - page 211

explained by better trapping of drug within polymeric spherulites with the more rapid
rates of PHB crystallization at 110°C [113, 114].
Kawaguchi T. et al showed that chemical properties of drug and polymer mo-
lecular weight had a great impact on drug delivery kinetics from PHB matrix. Mi-
crospheres (100-300 —m in diameter) from PHB of different molecular weight (65,
135, and 450 kDa) were loaded with prodrugs of 5-À uoro-2'deoxyuridine (FUDR)
synthesized by esteri¿ cation with aliphatic acids (propionate, butyrate, and pentano-
ate). Prodrugs have different physico-chemical properties, in particular, solubility in
water (from 70 mg/ml for FUDR to 0.1 mg/ml for butyryl-FUDR). The release rates
from the spheres depended on both the lipophilicity of the prodrug and the molecu-
lar weight of the polymer. Regardless of the polymer, the relative release rates were
propionyle-FUDR>butyryl- FUDR>pentanoyl-FUDR. The release of butyryl- FUDR
and pentanoyl-FUDR from the spheres consisting of low-molecular-weight polymer
(M w = 65 kDa) was faster than that from the spheres of higher molecular weight (M w
= 135 or 450 kDa). The effect of drug content on the release rate was also studied. The
higher the drug content in the PHB microspheres, the faster was the drug release. The
release of FUDR continued for more than 5 days [58].
Kassab A. C. developed a well-managed technique for manufacture of PHB mi-
crospheres loaded with drugs. Microspheres were obtained within a size of 5-100
—m using a solvent evaporation method by changing the initial polymer/solvent ratio,
emulsi¿ er concentration, stirring rate, and initial drug concentration. Very high drug
loading of up to 408 g rifampicin/g PHB were achieved. Drug release rates were rapid:
the maximal duration of rifampicin delivery was 5 days. Both the size and drug con-
tent of PHB microspheres were found to be effective in controlling the drug release
from polymer microspheres [118].
The sustained release of analgesic drug, tramadol, from PHB microspheres was
demonstrated by Salman M. A. et al. It was shown that 58% of the tramadol (the initial
drug content in PHB matrix = 18%) was released from the microspheres (7.5 —m in
diameter) in the ¿ rst 24 hr. Drug release decreased with time. From 2 to 7 days the
drug release was with zero order rate. The entire amount of tramadol was released after
7 days [128].
The kinetics of different drug release from PHB ¿ lms and microspheres was stud-
ied by our team [24, 127]. It was found that the release occurs via two mechanisms,
diffusion and degradation, operating simultaneously. Vasodilator and antithrombotic
drug, dipyridamole, and anti-inÀ ammatory drug, indomethacin, diffusion processes
determine the rate of the release at the early stages of the contact of the system with
the environment (the ¿ rst 6-8 days). The coef¿ cient of the release diffusion of a drug
depends on its nature, the thickness of the PHB ¿ lms containing the drug, the weight
ratio of dipyridamole and indomethacin in polymer, and the molecular weight of PHB.
Thus, it is possible to regulate the rate of drug release by changing of molecular weight
of PHB, for example. A number of other drugs have been also used for development
polymeric systems of sustained drug delivery: antibiotics (rifampicin, metronidazole,
ciproÀ oxacin, levoÀ oxacin), anti-inÀ ammatory drugs (À urbiprofen, dexamethasone,
prednisolone), and antitumor drugs (paclitaxel) [127]. The biodegradable micro-
spheres on the base of PHB designed for controlled release of dipyridamole were