Crystallisation of estradiol containing TDDS determined by isothermal microcalorimetry, X-ray diffraction, and optical microscopy

Latsch, Silvia; Selzer, Torsten; Fink, Lothar; Kreuter, Jörg

doi:10.1016/s0939-6411(03)00042-0

Cited by 27 publications

(13 citation statements)

References 34 publications

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“…Furthermore, the equilibrium saturation solubility in the acceptor layer, c s *, is substantially larger at the higher temperature. The more rapid attainment of equilibrium can be explained by higher diffusivity, D [cm 2 /s], of the scopolamine within the polymer layers of DURO-TAK 87-2677. This has been demonstrated by simulations using a numerical solution to this 3-layer diffusional problem 4 .…”

Section: Resultsmentioning

confidence: 99%

“…There are various experimental methods available to determine the saturated solubility, including detecting of crystalline drug in the polymer film using light microscopy, differential scanning calorimetry, wide-angle X-ray diffraction, infra-red or Raman spectroscopy, measurement of drug release rate, crystal seeding, and drug uptake from a liquid solution or a solid solution 1 . Most of these techniques encompass the danger of supersaturation of the polymer film with the drug and a resulting over-estimation of saturation solubility value 2 .…”

Section: Introductionmentioning

confidence: 99%

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Untitled

2016

IJPSR

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ABSTRACT:The method of drug uptake from solid solution has been used to measure the saturation solubility of scopolamine base in various pressure sensitive adhesive DURO-TAKs at elevated temperature. The saturation solubility was strongly temperature dependent, being 50 -100 % larger at 45°C than at 25°C. The higher temperature also caused much more rapid approach to equilibrium distribution of the drug between donor, separating membrane, and acceptor layers. With a cross-linked DURO-TAK 87-2677 the saturation solubility is 10.7 ± 0.30 % (n=4) at 25 °C, rising to 16.5 ± 0.54 % at 45 °C (n=4). The non-cross-linked DURO-TAK 87-4098 gives lower values of 6.3 ± 0.27% w/w(n=4) at 25 °C, rising to 13.2 ± 1.14 % at 45 °C. The hydrophobic DURO-TAK 87-2510gives the lowest values of 4.2 ± 0.17 % w/w (n=4) at 25 °C and 8.7 ± 0.45 % (n=4) at 45°C. The thermodynamic activity of the drug in the thin polymer film will therefore decrease as temperature increases.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Untitled

2016

IJPSR

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“…However, inclusion of the polymer into the crystalline structure of estradiol is not probable which can be confirmed using the findings of Latsch also Iervolino (10,17). Latsch et al, investigating of estradiol hemihydrate crystallization by X-ray powder diffraction, could not detect any evidence that the amorphous acrylate-vinyl acetate copolymer matrix had an effect on the crystal structure (10). Also, according to the findings reported by Iervolino et al, the polymer molecules cannot become included into the Ibuprofen crystals due to their incompatibility in size (17).…”

Section: Discussionmentioning

confidence: 95%

“…Nucleation is often regarded as a decisive step in crystallization process and the number of molecules necessary to achieve a nucleating cluster is inversely proportional to the degree of supersaturation (7). Estradiol has a pronounced tendency for crystallization (8) and its crystallization in acrylic adhesives has been reported both after evaporation of the adhesive solvents during the drying stage of process (6) or storage period (8)(9)(10). It should be noted that the most characteristic property of estradiol is its tendency to adopt the hemihydrated form (Fig.…”

Section: Introductionmentioning

confidence: 99%

Effect of Adhesive Layer Thickness and Drug Loading on Estradiol Crystallization in a Transdermal Drug Delivery System

et al. 2010

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Abstract. The effects of adhesive layer thickness and drug loading on estradiol crystallization were studied in a drug-in-adhesive patch. Patches containing different estradiol loadings (1.1% and 1.6% w/w) in different thicknesses (45, 60, and 90 μm) were prepared by coating of a homogenous mixture of adhesive solution and the drug on a siliconized release liner by a film applicator. After drying, the film was laminated on a Poly(ethylene terephthalate) backing layer and cut into appropriate size. Release tests were performed using thermostated Chien-type diffusion cells. Cross-section of the patches was observed by optical microscopy. Scanning electron microscopy was done for surface analysis of the patches after drug release test. Crystal formation was not expected in the adhesive layer based on the linear free-energy relationship formalisms however; crystalline regions were observed in different locations through the thickness of the patches. These regions were significantly more discontinuous in 45 μm samples which elucidated the effective role of adhesive layer thickness in drug crystallization. Extensive crystallization observed for thicker patches was attributed to the strong crosslinking capability of estradiol hemihydrate. Drug release study confirmed some of the crystallization results. No significant increase was observed in the burst release with increasing in thickness from 45 to 60 μm which can be attributed to the severe increase in the crystallization extent. Also, formation of a crystalline layer near the releasing surface and more discontinuous pattern of the crystals in some samples was confirmed by investigation of the drug release curves.

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“…In contrast to the case of amorphous indomethacin (Bhugra et al 2008), the induction of estradiol crystallization from polymeric patches was detected quite earlier by IMC than by microscopy. Likewise, crystallization kinetics from a low amount of amorphous norethindrone acetate dispersed in a transdermal polymeric patch was studied using IMC (Latsch et al 2003). The crystallization from the patch containing 4 %w/w drug was detected more by IMC than by microscopy.…”

Section: Crystallization Kinetics Of and Crystallinity In Amorphous Smentioning

confidence: 99%