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ABSTRACT: The reasons for retarded release of naproxen sodium from the chitosan matrices at different pH include poor aqueous solubility of drug, the formation of a rate-limiting polymer gel barrier along the periphery of matrices, the interaction of naproxen sodium with protonated amino groups of chitosan, and the interaction of ionized amino groups of chitosan with ionized sulfate groups of kappa-carrageenan.
AAPS PharmSciTech 02/2007; 8(2):Article 44. · 1.43 Impact Factor
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ABSTRACT: The study investigates ibuprofen with wax-like properties as a multifunctional agent (as an active component and as a melt binder). Binding efficiency was compared with granules prepared by wet granulation using polyvinylpyrollidone (PVP K-30) as a binder for micromeritic, physical and mechanical properties such as angle of repose, particle size distribution Carr's index, Hausner's ratio, crushing strength, percentage fines, Heckel plot study and tensile strength. To check the binder distribution during melt granulation, the content uniformity was determined. To check changes in the physical state of ibuprofen, XRPD, DSC and FTIR studies were carried out. The present study underlines the fact that ibuprofen may be adopted as a binder in ibuprofen formulations using the melt granulation technique.
Acta Pharmaceutica 12/2006; 56(4):451-61. · 0.91 Impact Factor
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ABSTRACT: Single and multi-unit floating matrices of risedronate sodium were prepared using Gelucire 43/01 by melt solidification and melt granulation technique, respectively. The controlled release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Effect of aging on Gelucire 43/01 was evaluated by hot stage microscopy (HSM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), in vitro floating ability, and in vitro drug release. Multi-unit system obtained has shown initial burst release, which was suppressed in single unit system. Both single- as well as multi-unit systems showed increase in rate of drug release on aging due to changes in the properties of the Gelucire 43/01. Multi-unit matrices obtained by melt granulation were relatively easier for scale up and advantageous if the initial burst release does not cause any significant clinical adversity.
Drug Development and Industrial Pharmacy 11/2005; 31(9):851-60. · 1.49 Impact Factor
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ABSTRACT: Solid dispersions (SDs) of glibenclamide (GBM); a poorly water-soluble drug and polyglycolized glycerides (Gelucire with the aid of silicon dioxide (Aerosil 200); as an adsorbent, were prepared by spray drying technique. SDs and spray dried GBM in comparison with pure GBM and corresponding physical mixtures (PMs) were initially characterized and then subjected to ageing study up to 3 months. Initial characterization of SDs and spray dried GBM by DSC and XRPD showed that GBM was present in its amorphous form (AGBM). Improvement in the solubility and dissolution rate was observed for all samples. DRIFT spectroscopy revealed presence of hydrogen bonding in SDs. During ageing study, almost no decrease of in vitro drug dissolution was observed, over the period of 3 months as compare with freshly prepared SDs. Slight crystallinity in SDs was observed in the DSC and XRPD studies during ageing. Moreover in vivo study in Swiss Albino mice also justified the improvement in the therapeutic efficacy of amorphous GBM in SDs over pure GBM. Thus, present study demonstrated the high potential of spray drying technique for obtaining stable free flowing SDs of poorly water-soluble drugs using polyglycolized glycerides carriers with the aid of silicon dioxide as an adsorbent.
European Journal of Pharmaceutical Sciences 11/2005; 26(2):219-30. · 3.21 Impact Factor
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ABSTRACT: Amorphous drugs have gained importance because of their advantageous biopharmaceutical properties; however, their stabilization remains a challenge. The purpose of this work was to stabilize the amorphous form of etoricoxib (ET) by using a low excipient/drug ratio to improve drug dissolution and thus bioavailability.
The effect of Gelucire and polyvinylpyrrolidone (PVP) on stabilization and bioavailability of amorphous etoricoxib (AET) was studied. X-ray powder diffractometry, differential scanning calorimetry, and scanning electron microscopy were used to study the physical state of the drug. Dissolution studies were performed for melt granules of AET with Gelucire 50/13 (MG-AET) and solid dispersion with PVP (SDP) to differentiate dissolution performance. A stability study on samples was conducted for 3 months to evaluate the physical state of the drug and its dissolution in the formulation. The in vivo performance of the optimized and stable formulation of ET was evaluated in rat.
Dissolution of MG-AET was significantly improved as compared to AET and SDP. Both factors, amorphization of drug and melt granulation with lipid, seemed to be important for improving dissolution. Stability data revealed that MG-AET was significantly advantageous for AET stabilization, whereas PVP was not. The amount of Gelucire required for the stabilization of one part of AET was 0.5 part (by weight), whereas even 1.5 part (by weight) of PVP failed to elicit the same result. The superior in vivo performance of MG-AET has been attributed to the altered physiochemical properties of AET and the presence of lipid in the system.
Gelucire can stabilize AET and improve its biopharmaceutical performance at a low excipient/drug ratio and may provide a better alternative to conventional stabilizers such as PVP.
Pharmaceutical Research 11/2005; 22(10):1727-34. · 4.09 Impact Factor
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ABSTRACT: The objective of this review article is to explain the use of cyclodextrin in the different routes of drug administration. The article gives the chemistry of cyclodextrins and addresses the issue of the mechanism of drug release from cyclodextrin complexes. Dilution, competitive displacement, protein binding, change in ionic strength and temperature and drug uptake by tissues are the different release mechanisms of the drug from the drug-cyclodextrin complex discussed here. Use and its limitations in the different drug delivery systems like nasal, ophthalmic, transdermal and rectal drug delivery are explained. The application of the cyclodextrins in the oral drug delivery is detailed in this review. Many studies have shown that cyclodextrins are useful additives in the different routes of drug administration because of increased aqueous solubility, stability, bioavailability and reduced drug irritation.
Acta Pharmaceutica 07/2005; 55(2):139-56. · 0.91 Impact Factor
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ABSTRACT: The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions suggests the transformation of crystalline etoricoxib into an amorphous form. In the HSM examination of solid dispersions, the dissolution of drug in the lipid carriers was observed, which was also confirmed by the absence of etoricoxib peak in DSC curves of solid dispersions. The DRIFTS spectra revealed the presence of hydrogen bonding in solid dispersions. The in vitro dissolution test showed a significant increase in the dissolution rate of solid dispersions as compared with pure etoricoxib, spray-dried etoricoxib, and physical mixtures of drug with lipid carriers. Therefore, the dissolution rate of poorly water-soluble drug etoricoxib can be significantly enhanced by the preparation of solid dispersions using lipid carriers by spray drying technique.
AAPS PharmSciTech 02/2005; 6(3):E405-12. · 1.43 Impact Factor
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ABSTRACT: Incorporation of bisphosphonates in the lipid reduces gastric irritation. Only gastric retention with sustained release allows the drug to reach the duodenum and jejunum and improves the availability of bisphosphonates. Risedronate sodium and Gelucire 39/01 floating matrices were prepared using melt solidification. The sustained release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Ageing of the matrices was studied by differential scanning calorimetry, hot stage polarizing microscopy, scanning electron microscopy and in vitro drug release. Ageing causes changes in the crystal structure of Gelucire, which is responsible for an increase in drug release.
Acta Pharmaceutica 10/2004; 54(3):205-14. · 0.91 Impact Factor
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ABSTRACT: The basic objective of this study was to explore the application of Gelucire 43/01 for the design of multi-unit floating systems of a highly water-soluble drug diltiazem HCl. Diltiazem HCl-Gelucire 43/01 granules were prepared by melt granulation technique. The granules were evaluated for in vitro and in vivo floating ability, surface topography, and in vitro drug release. Aging effect on storage was evaluated using scanning electron microscopy, hot stage polarizing microscopy (HSPM), differential scanning calorimetry (DSC), and in vitro drug release. Granules were retained in stomach at least for 6 hours. Approximately 65% to 80% drug was released over 6 hours with initial fast release from the surface. Surface topography, HSPM, DSC study of the aged samples showed phase transformation of Gelucire. The phase transformation also caused significant increase in drug release. In conclusion, hydrophobic lipid, Gelucire 43/01, can be considered as an effective carrier for design of a multi-unit floating drug delivery system of highly water-soluble drugs such as diltiazem HCl.
AAPS PharmSciTech 02/2004; 5(3):e43. · 1.43 Impact Factor
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ABSTRACT: The basic objective of this work was to study the effect of model cationic drug metformin HCl on swelling and erosion and, in turn, the release of KCl and drug itself, from the kappa-carrageenan matrices. Water uptake by the matrix up to 2 hours was found to increase with KCl concentration from the plain matrix. Erosion was not affected by concentration of KCl. Incorporation of drug favors water uptake, but in presence of KCl it was found to be reduced. Drug-containing matrices have shown higher release of KCl as compared with plain batches. Drug release was retarded as KCl concentration increased up to 5%, above which the reduced cohesivity of the matrix caused increase in drug release.
AAPS PharmSciTech 02/2004; 5(2):e25. · 1.43 Impact Factor
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ABSTRACT: A melt solidification technique has been developed to obtain sustained-release waxy beads of flurbiprofen. Low glass transition temperature (t(g)) and shear-induced crystallization of flurbiprofen made it a suitable candidate for melt solidification technique. The process involved emulsification and solidification of flurbiprofen-cetyl alcohol melt at significantly low temperature (5 degrees C). The effect of variables, namely, the amount of cetyl alcohol and the speed of agitation, was studied using 3(2)factorial design. The technique and the beads were evaluated on the basis of process and desired yield, surface topography, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), particle size distribution, crushing strength, and drug release. Average values for process and desired yields were 97% wt/wt and 26% wt/wt, respectively. No interaction was observed between drug and excipient. Multiple regression analysis was carried out, and response surfaces were obtained. A curvilinear relationship was observed between percentage of desired yield and the amount of cetyl alcohol. Linear decrease in crushing strength was observed with increase in the amount of cetyl alcohol. Drug released from the beads followed zero order kinetics. Burst release was shown to a greater extent in beads containing a lower amount of cetyl alcohol. Response surfaces of time required for certain percentage of drug (t(D)%) showed that after critical concentration of about 20% of cetyl alcohol (400 mg/batch), no significant release retardant effect was observed.
AAPS PharmSciTech 01/2004; 4(4):E65. · 1.43 Impact Factor
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ABSTRACT: Ibuprofen (IBU) exhibits short half-life, poor compressibility, flowability and caking tendency. IBU melt has sufficiently low viscosity and exhibits interfacial tension sufficient to form droplet even at low temperature. A single step novel melt solidification technique (MST) was developed to produce IBU beads with lower amounts of excipient. Effect of variables was studied using a 3(2) factorial approach with speed of agitation and amount of cetyl alcohol (CA) as variables. The beads were evaluated using DSC, FT-IR and scanning electron microscope (SEM). Yield, micromeritic properties, crushing strength and release kinetics were also studied. Spherical beads with a method yield of above 90% were obtained. The data was analyzed by response surface methodology. The variables showed curvilinear relationship with yield in desired particle size range, crushing strength and, bulk and tap density. The drug release followed non-Fickian case II transport and the release rate decreased linearly with respect to amount of CA in the initial stages followed by curvilinearity at later stages of elution. The effect of changing porosity and tortuosity was well correlated.
International Journal of Pharmaceutics 09/2003; 261(1-2):57-67. · 3.35 Impact Factor
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ABSTRACT: A novel single step melt solidification technique was developed for ibuprofen. DSC studies designed to elucidate the effect of isothermal holding time showed that the extent of crystallization increased with holding time. Agitation speed and polyvinyl alcohol (PVA) were found to reduce the time required for crystallization. The excipient-free, non-disintegrating beads were irregular in shape with high mechanical strength and acceptable flowability. Slow dissolution from beads was attributed to the compactness and higher bond strength of the beads.
International Journal of Pharmaceutics 05/2003; 255(1-2):33-42. · 3.35 Impact Factor
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ABSTRACT: The study investigates ibuprofen with wax-like properties as a multifunctional agent (as an active component and as a melt binder). Binding efficiency was compared with granules prepared by wet granulation using polyvinylpyrollidone (PVP K-30) as a binder for micromeritic, physical and mechanical properties such as angle of repose, particle size distribution Carr’s index, Hausner’s ratio, crushing strength, percentage fines, Heckel plot study and tensile strength. To check the binder distribution during melt granulation, content uniformity was determined. To check changes in the physical state of ibuprofen, XRPD, DSC and FTIR studies were carried out. The present study underlines the fact that ibuprofen may be adopted as a binder in ibuprofen formulations using the melt granulation technique
Acta pharmaceutica (hfd-fg-ap@zg.htnet.hr); Vol.56 No.4.
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ABSTRACT: The objective of this review article is to explain the use of cyclodextrin in the different routes of drug administration. The article gives the chemistry of cyclodextrins and addresses the issue of the mechanism of drug release from cyclodextrin complexes. Dilution, competitive displacement, protein binding, change in ionic strength and temperature and drug uptake by tissues are the different release mechanisms of the drug from the drug-cyclodextrin complex discussed here. Use and its limitations in the different drug delivery systems like nasal, ophthalmic, transdermal and rectal drug delivery are explained. The application of the cyclodextrins in the oral drug delivery is detailed in this review. Many studies have shown that cyclodextrins are used as useful additives in the routes of drug administration because of increased aqueous solubility, stability, bioavailability and reduced drug irritation.
Acta pharmaceutica (hfd-fg-ap@zg.htnet.hr); Vol.55 No.2.
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ABSTRACT: Incorporation of bisphosphonates in the lipid reduces gastric irritation. Only gastric retention with sustained release allows the drug to reach the duodenum and jejunum and improves the availability of bisphosphonates. Risedronate sodium and Gelucire® 39/01 floating matrices were prepared using melt solidification. The sustained release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Ageing of the matrices was studied by differential scanning calorimetry, hot stage polarizing microscopy, scanning electron microscopy and in vitro drug release. Ageing causes changes in the crystal structure of the Gelucire®, which is responsible for increase in drug release.
Acta pharmaceutica (hfd-fg-ap@zg.htnet.hr); Vol.54 No.3.
