RESUMEN
Glibenclamide (GLIB) is a poorly soluble drug with formulation-dependent bioavailability. Therefore, we attempted in this study to improve GLIB dissolution rate by preparing drug solid dispersions by solvent evaporation (SE) and supercritical fluid solvent-antisolvent techniques (SCF-SAS). A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE. The ratios of carriers used in SCF-SAS method were HPMCE5 (fixed at 60%), PEG6000 (20-40%), and Poloxamer407 (0-20%). A constant drug: carrier weight ratio of 1:10 was used in all experiments. The SDs obtained were physically characterized and subjected to the dissolution study. The major GLIB bands in FTIR spectra were indicative of drug integrity. The reduced intensity and the fewer number of peaks observed in X-ray diffractograms (XRD) of GLIB formulations was the indicative of at least partial transformation of crystalline to amorphous GLIB. This change and/or dilution of drug in much higher amounts of carriers present caused disappearance of distinctive endothermic peaks in differential scanning calorimetry thermograms of GLIB formulations. The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances. As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix.
RESUMEN
The interaction of drugs and polymers used to incorporate in or surface modify/coat the liposomes can affect the phase transition, fluidity and other physical properties as well as in vivo fate of vesicles. In this study, differential scanning calorimetry (DSC) was used to investigate changes in the temperature and the enthalpy of phase transition of liposomes of various electrical charges following interaction with carboxymethyl chitin (CM-chitin) as a hydrophilic polymer, cholesterol-derivatized mannan (CHM) as a hydrophilic polymer bearing a hydrophobic moiety, and insulin as a model peptide. The results indicated that insulin incorporation or polymers caused no significant change in the phase transition temperature (T(m)) of liposomes. However, reduction in the enthalpy of the transition (ΔH°) following coating with CHM supports an anchoring mechanism to the bilayer by the polymer, whereas no change or little increase in the ΔH° after coating with carboxymethyl chitin suggests no significant interaction or electrostatic weak interactions of polymer with liposomes. The DSC data of liposome-polymer interaction may be suggestive of changes in membrane fluidity, drug release, and possibly the behavior of liposomes in biological milieu.
RESUMEN
Cinnarizine (CN) is a pipperazine derivative with anti-histaminic activity and high affinity to H(1) receptors. The objective of this study was to produce floating microspheres (FM) of CN by diffusion solvent evaporation technique to increase drug solubility and hence its bioavailability. The effect of process variables such as: Eudragit type, stirring rate and time of stirring after addition of oily phase to the aqueous phase were evaluated on the yield, particle size, loading, release and floating behaviors of microspheres using a factorial design. Release of CN from microspheres was studied in pHs: 1.2 and 7.2 using paddle technique. The samples of dissolution test were analysed spectrophotometrically at 256.1 nm and 256.5 nm respectively. particle size of microspheres was studied using microscopic method and their floating behavior was studied in HCl (0.1 N, pH 1.2) medium with Tween 20 (0.5% w/v). Eight formulations were produced by changing 3 variables each at 2 levels: Eudragit S100 (Ps) or a combination of two Eudragits S100:RLPO (1:3) (P(SR)), stirring rate of 200 (R(2)) or 300 rpm (R(3)) and stirring time after addition of oily phase to the aqueous phase 0 (T(0)) or 1 hr (T(1)). The average size of microspheres was 300 microm. The highest yield efficiency (94%) was seen in P(SR)R(3)T(0) formulation and the greatest loading percentage was 8.5% in P(SR)R(2)T(1) formulation. The microspheres containing just Eudragit S100, didn't show suitable releasing profile during 8 hours in pH 1.2 but those containing combination of Eudragit S100:RL released approximately whole amount of CN during 10 hours (8 hours in pH 1.2 and 2 hours in pH 7.2). The highest floating percentage up to 6 hours was 77.5% in P(S)R(2)T(1) formulation. The type of Eudragit used seems to play an important role in producing sustained release floating microspheres. P(SR)R(3)T(0) formulation containing both types of Eudragit S100:RL (1.3) that releases 99.1% of the drug after 10 hours and 65% floating after 6 hr seems suitable for oral sustained delivery of CN.
