New Trends in Polymers - Progress in Organic and Physical Chemistry: Structures and Mechanisms - page 210

months), that provides effective pharmaceutical action. At curative dose the prolonged
delivery of drugs from the systems into organism permits to eliminate the shortcom-
ings in peroral, injectable, aerosol, and the other traditional methods of drug admin-
istration. Among those shortcomings hypertoxicity, instability, pulsative character of
rate delivery, ineffective expenditure of drugs should be pointed out. Alternatively,
applications of therapeutical polymer systems provide orderly, and purposefully the
deliverance for an optimal dose of agent that is very important at therapy of acute or
chronic diseases [108]. An ideal biodegradable microsphere formulation would con-
sist of a free-flowing powder of uniform-sized microspheres less than 125 ȝm in diam-
eter and with a high drug loading. In addition, the drug must be released in its active
form with an optimized release profile. The manufacturing method should produce
such microspheres in a process that is reproducible, scalable, and benign to some often
delicate drugs, with high encapsulation efficiency [109, 110].
The PHB as biodegradable and biocompatible is a promising material for produc-
ing of polymer systems for controlled drug release. A number of drugs with vari-
ous pharmacological activities were used for development of polymer controlled
release systems on the base of PHA, mainly on the base of poly(3-hydroxybutyrate-
co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-4- hydroxybutyrate) copoly-
mers: model drugs (2,7-dichloroÀ uorescein [111], dextran-FITC [112], methyl red
[113, 114], 7-hydroxethyltheophylline [115, 116]), antibiotics and antibacterial drugs
(rifampicin [117, 118], tetracycline [119], cefoperazone and gentamicin [120], sulp-
erazone. and duocid [121-124], sulbactam and cefoperazone [125]), anticancer drugs
(5-À uorouracil [126], 2',3'-diacyl-5-À uoro-2'-deoxyuridine [58]), anti-inÀ ammatory
drug (indomethacin [127]), analgesics (tramadol [128]), vasodilator, and antithrom-
botic drugs (dipyridamole [24, 127, 129], NO donor [130, 131]). The biocompatibil-
ity and pharmacological activity of some of these systems was studied [24, 58, 117,
123-125, 128, 131]. But only a few drugs were used for production of drug controlled
release systems on the base of PHB homopolymer: 7-hydroxethyltheophylline, methyl
red, 2',3'-diacyl-5-À uoro-2'-deoxyuridine, rifampicin, tramadol, indomethacin, and
dipyridamole [58, 113-118, 127-131].
The ¿ rst drug sustained delivery system on the base of PHB was developed by
Korsatko W. et al., who observed a rapid release of encapsulated drug, 7-hydroxethyl-
theophylline, from tablets of PHB (M w = 2000 kDa), as well as weight losses of PHB
tablets containing the drug after subcutaneous implantation. It was suggested that PHB
with molecular weight greater than 100 kDa was undesirable for long-term medication
dosage [115].
Pouton C.W. and Akhtar S. describing the release of low molecular drugs from
PHB matrices reported that the latter have the tendention of enhanced water penetra-
tion and pore formation [132]. The entrapment and release of model drug, methyl red,
from melt-crystallized PHB matrices was found to be a function of polymer crystal-
lization kinetics and morphology whereas overall degree of crystallinity was shown
to cause no effect on drug release kinetics. Methyl red released from PHB ¿ lms for
more than 7 days with initial phase of rapid release (“burst effect”) and second phase
with relatively uniform release. Release pro¿ les of PHB ¿ lms crystallized at 110ÛC
exhibited a greater burst effect when compared to those crystallized at 60ÛC. This was