[ Pobierz całość w formacie PDF ]
drying at 708C for 6 h. XRPD analysis revealed
Sugimoto et al.102 led an extensive study on that a small percentage of original crystalline
bioavailability enhancement of Nifedipine (low drug still existed in the coground system.
water soluble ( 5 mg/mL, pH 5.5, 308C103) Figure 11A shows the in vitro nifedipine release
DOI 10.1002/jps JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 98, NO. 11, NOVEMBER 2009
3982 COLOMBO, GRASSI, AND GRASSI
huge increase of Cmax (89 ng/mL, coground
system; 9.1 ng/mL, physical mixture) and AUC
(122 ng h/mL, coground system; 47 ng h/mL,
physical mixture) proved the neat bioavailability
improvement due to activation. Interestingly, the
authors noted that if water was not added to the
ternary system, drug activation was not equally
pronounced.
Antispasmodic Drugs
Sawayanagi et al.104 studied the mechanochem-
ical activation of phenytoin by cogrinding it
with chitin or chitosan. They found that a 1:2
Phenytoin: chitosan coground mixture orally
administered to beagle dogs comported a sub-
stantial increase in phenytoin blood concentra-
tion. In particular, the AUC corresponding to
activated drug was approximately three times
that of native phenytoin and that maximum drug
concentration was roughly 3.2 times that compet-
ing to the native drug. Similar encouraging
results were also found for mechanochemical
activation of phenytoin in presence of cellulose
(1:9 drug:polymer ratio). Interestingly, in vitro
dissolution tests indicated a neatly higher dis-
solution rate in comparison with that of the native
drug.16
Figure 11. (A) In vitro test referring to nifedipine
Antifungal Drugs
release from activated nifedipine polyethylene glycol
6000 hydroxypropylmethyl cellulose (1:1:5 (w/w) ratio)
The mechanochemical activation of griseofulvin in
system (filled circles). Almost all the original drug is
mixture with different polymeric carriers (potato
amorphous. Open circles indicate the release behaviour
starch, polyethylene glycol, chitosan) led to
of an equal w/w ratio physical mixture that did not
improved in vitro dissolution characteristic with
undergo cogrinding (activation). t is time. (B) Compar-
respect to that of the native drug.16 This promis-
ison between in vivo behaviour referring to the acti-
ing in vitro behaviour reflected in good in vivo
vated system (filled circles) and the same w/w ratio
results. Indeed, experiments conducted on rats
physical mixture (open circles). C is blood concentration
while t is time. and rabbits, demonstrated an increase of bioavail-
ability equal to 40% and 50%, respectively
(vibrational mill, drug/polymer ratio ranging
(JP paddle method, 900 mL water, 378C, stirring from 1:2 to 2.1). Interestingly, urinary excretion
100 rpm) referring to the activated system (filled tests allowed verifying that the increased
circles) and the identical physical mixture (open griseofulvin concentration was due to an increase
circles). Also in this case, the better performance of the (pharmacokinetic) absorption constant as
of the activated system results evident. This the (pharmacokinetic) elimination constant was
interesting in vitro behaviour reflected into an substantially unaffected by mechanochemical
analogously interesting in vivo behaviour as activation.
witnessed by Figure 11B. This figure shows
nifedipine plasma concentration (beagle dogs)
following oral administration (by means of a CONCLUSIONS
sonde) of 50 mL water suspension containing an
amount of activated system (filled circles) or the Mechanochemical activation represents a
same amount of physical mixture (open circles) versatile and valuable tool to improve drug
corresponding to a dose of 10 mg nifedipine. The bioavailability. The versatile aspect relies in
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 98, NO. 11, NOVEMBER 2009 DOI 10.1002/jps
DRUG MECHANOCHEMICAL ACTIVATION 3983
the possibility of properly tuning the activation 6. Butyagin PY. 1989. Active states in mechanochem-
ical reactions. Glasgow: Hardwood Acad. Publ.
conditions such as carrier type, drug:carrier ratio,
7. Tká%0Å„ová K. 1989. Mechanical activation of
the possibility of contemporarily using more than
minerals. Amsterdam: Elsevier.
one carrier, milling time and milling type
8. Juhasz AZ, Opoczky L. 1990. Mechanical activa-
(determining the amount and rate of energy
tion of minerals by grinding. Budapest: Akademiai
transfer to the coground system) and the possi-
Kiado.
bility of using water to favour the activation
9. Shingo PH, editor. 1992. Mechanical alloying. Zür-
process. The valuable aspect consists in the huge
ich: Trans. Tech. Publications.
drug bioavailability improvement that this
10. Gutman EM. 1994. Mechanochemistry of solid
approach can ensure without recurring to the
surfaces. London: World Scientific. [ Pobierz całość w formacie PDF ]
zanotowane.pl doc.pisz.pl pdf.pisz.pl szkicerysunki.xlx.pl
drying at 708C for 6 h. XRPD analysis revealed
Sugimoto et al.102 led an extensive study on that a small percentage of original crystalline
bioavailability enhancement of Nifedipine (low drug still existed in the coground system.
water soluble ( 5 mg/mL, pH 5.5, 308C103) Figure 11A shows the in vitro nifedipine release
DOI 10.1002/jps JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 98, NO. 11, NOVEMBER 2009
3982 COLOMBO, GRASSI, AND GRASSI
huge increase of Cmax (89 ng/mL, coground
system; 9.1 ng/mL, physical mixture) and AUC
(122 ng h/mL, coground system; 47 ng h/mL,
physical mixture) proved the neat bioavailability
improvement due to activation. Interestingly, the
authors noted that if water was not added to the
ternary system, drug activation was not equally
pronounced.
Antispasmodic Drugs
Sawayanagi et al.104 studied the mechanochem-
ical activation of phenytoin by cogrinding it
with chitin or chitosan. They found that a 1:2
Phenytoin: chitosan coground mixture orally
administered to beagle dogs comported a sub-
stantial increase in phenytoin blood concentra-
tion. In particular, the AUC corresponding to
activated drug was approximately three times
that of native phenytoin and that maximum drug
concentration was roughly 3.2 times that compet-
ing to the native drug. Similar encouraging
results were also found for mechanochemical
activation of phenytoin in presence of cellulose
(1:9 drug:polymer ratio). Interestingly, in vitro
dissolution tests indicated a neatly higher dis-
solution rate in comparison with that of the native
drug.16
Figure 11. (A) In vitro test referring to nifedipine
Antifungal Drugs
release from activated nifedipine polyethylene glycol
6000 hydroxypropylmethyl cellulose (1:1:5 (w/w) ratio)
The mechanochemical activation of griseofulvin in
system (filled circles). Almost all the original drug is
mixture with different polymeric carriers (potato
amorphous. Open circles indicate the release behaviour
starch, polyethylene glycol, chitosan) led to
of an equal w/w ratio physical mixture that did not
improved in vitro dissolution characteristic with
undergo cogrinding (activation). t is time. (B) Compar-
respect to that of the native drug.16 This promis-
ison between in vivo behaviour referring to the acti-
ing in vitro behaviour reflected in good in vivo
vated system (filled circles) and the same w/w ratio
results. Indeed, experiments conducted on rats
physical mixture (open circles). C is blood concentration
while t is time. and rabbits, demonstrated an increase of bioavail-
ability equal to 40% and 50%, respectively
(vibrational mill, drug/polymer ratio ranging
(JP paddle method, 900 mL water, 378C, stirring from 1:2 to 2.1). Interestingly, urinary excretion
100 rpm) referring to the activated system (filled tests allowed verifying that the increased
circles) and the identical physical mixture (open griseofulvin concentration was due to an increase
circles). Also in this case, the better performance of the (pharmacokinetic) absorption constant as
of the activated system results evident. This the (pharmacokinetic) elimination constant was
interesting in vitro behaviour reflected into an substantially unaffected by mechanochemical
analogously interesting in vivo behaviour as activation.
witnessed by Figure 11B. This figure shows
nifedipine plasma concentration (beagle dogs)
following oral administration (by means of a CONCLUSIONS
sonde) of 50 mL water suspension containing an
amount of activated system (filled circles) or the Mechanochemical activation represents a
same amount of physical mixture (open circles) versatile and valuable tool to improve drug
corresponding to a dose of 10 mg nifedipine. The bioavailability. The versatile aspect relies in
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 98, NO. 11, NOVEMBER 2009 DOI 10.1002/jps
DRUG MECHANOCHEMICAL ACTIVATION 3983
the possibility of properly tuning the activation 6. Butyagin PY. 1989. Active states in mechanochem-
ical reactions. Glasgow: Hardwood Acad. Publ.
conditions such as carrier type, drug:carrier ratio,
7. Tká%0Å„ová K. 1989. Mechanical activation of
the possibility of contemporarily using more than
minerals. Amsterdam: Elsevier.
one carrier, milling time and milling type
8. Juhasz AZ, Opoczky L. 1990. Mechanical activa-
(determining the amount and rate of energy
tion of minerals by grinding. Budapest: Akademiai
transfer to the coground system) and the possi-
Kiado.
bility of using water to favour the activation
9. Shingo PH, editor. 1992. Mechanical alloying. Zür-
process. The valuable aspect consists in the huge
ich: Trans. Tech. Publications.
drug bioavailability improvement that this
10. Gutman EM. 1994. Mechanochemistry of solid
approach can ensure without recurring to the
surfaces. London: World Scientific. [ Pobierz całość w formacie PDF ]