Effect of polymers on crystallo-co-agglomeration of ibuprofen-paracetamol: Factorial design

Liu

Crystal Growth & Design

et al. 2014

Pulmonary inhalation is increasingly being selected as a preferred route for the delivery of both small and large drug macromolecules for the treatment of a range of pathologies. The direct crystallization of micronized powders, in particular, paracetamol, remains difficult, as it requires the ability to work in high solution supersaturations where agglomeration, wall crusting, and heterogeneous nucleation hinder the control of crystal size and crystal size distribution. Polymer additives are recognized to help drive the production of a given polymorph or controlling crystal shape by means of adsorption on the crystal surface. With the aim of exploiting the polymer-control nucleation and growth of crystals for enhanced direct crystallization of micronized powders, batch cooling crystallization of paracetamol in water was carried out in the presence of 0.1−0.8% w/w hydroxypropyl methylcellulose (HPMC). In the presence of polymer, the onset of nucleation was delayed and extended beyond the cooling time of the solution, resulting in an isothermal cooling crystallization and the production of micronized paracetamol with a mean crystal size D 50 , in the range of 15−20 μm and an improved crystal size distribution. Equally, the rate generation of solution cloudiness was reduced by over 3-fold for the highest HPMC concentration tested, with no detectable impact on final product yield. The mechanisms for nucleation delay and growth inhibition by HPMC is unknown; however, a modification of crystal's shape observed upon the addition of HPMC to the solution suggested it might be related to mass transfer limitations and intermolecular hydrogen bonding between the large HPMC and the small drug molecules. This technique can potentially be used for direct crystallization of other micronized drugs.

Section: Introductionmentioning

confidence: 99%

Hydroxypropyl Methylcellulose as a Novel Tool for Isothermal Solution Crystallization of Micronized Paracetamol

Liu

Crystal Growth & Design

et al. 2014

“…As clear in Fig.3b which describe 3D-topography of crystalline asprin's surface no abnormal heights present on the whole scanned area 0.2x0.2 μm which reflects the quality of solution route synthesis as preparation technique for crystalline asprin even at very small area .These results indicate that the homogeneity degree are maximum with very small ratio of impurity phases as confirmed in XRD pattern recorded for crystalline asprin see Fig.1. Fig.3c shows deflection centers distribution of grain through scanned surface area 0.04 μm2 .As clear the in figure black dots refer to grain orientation on the surface which regularly distributed in circular arrangement reflect degree of homogeneity on the material surface .Only very few numbers of grains distributed irregularly due to jamming of population during re-crystallization process which affected by heating rate and solvent applied in crystallization process [12][13][14][15][16][17][18][19] .The connections of deflection dots could be benefit to understand both of micro-structural features and conduction mechanisms within material surface's. Fig.4 shows 3D-visualized image for crystalline asprin with maximum heights ranged in between 0.69-0.70 μm which represented by orangered color with ratio ~ 7% of total scanned area .The minimum depth with blue gradient color is nearly 18% recording 0.677-0.680 μm.…”

Section: Results and Discusionsmentioning

confidence: 99%

Soft Synthesis and Nano -Structural Features of Highly Crystalline Asprin An AFM-Investigations

Sekkina¹,

M.Elsabawya²,

El‐Maghraby³

2013

Orient. J. Chem

The present investigations introduce new trend of applying AFM-microscopy to visualize a real 3D-imaging of sample's surface topography. High resolution AFM-investigations indicated that crystalline asprin has regular arrays of atomic arrangement with no violation in the bulk of asprin .TM deflection AFM-gave us good approximation to the diffusion of grain throughout the surface topology of investigated asprin . The AFM-deflection centers imaging indicated that the numbers of grains distribute in circular arrangements on the surface and material bulk .3D-visualized imaging introduce precise determination of exposure surface area interacting with dissolving agent.

“…These might be due to the larger size of the agglomerates and better binding and close packing between crystals as a result of increased cohesive interaction between particles during agglomeration with polymers. [32] The presence of polymer also contributed to increase the strength agglomerates was also indicated in higher values of tensile strength [ Table 6]. Higher values for tensile strength of compacts of agglomerates compared to that of pure drug were sign of strong interparticulate bonding between the particles due to agglomeration in the presence of polymers.…”

Section: Resultsmentioning

confidence: 99%

“…Shape factor (P) and circularity factor (S) for the prepared agglomerates were obtained from the area (A) and perimeter (P') of the agglomerates using equations 12 and 13. [32] The photomicrographs of the agglomerates were taken, and tracings of the enlarged photomicrographs were used for the measurement of area and perimeter.…”

Section: Surface Topography and Sphericity Determinationmentioning

confidence: 99%

Untitled

Sorathia¹

2016

AJP

Purpose: The purpose of this study was to prepare sustained release (SR) spherical agglomerates with improved flow and compression properties using spherical crystallization technique. Methods: The spherical agglomerates of tiaprofenic acid were prepared by using quasi-emulsion solvent diffusion technique. Acetone and 0.1 N HCl were used as good solvent and poor solvent, respectively, while Eudragit RS100 and RL100 were used as release retardant polymers. The prepared agglomerates were evaluated for micromeritic, mechanical, and compression properties. Morphology and release characteristic of agglomerates was evaluated by scanning electron microscopy (SEM) analysis and in-vitro dissolution study, respectively. Differential scanning calorimetry (DSC) and Fourier transform-infrared (FT-IR) were performed to determine the presence of any drug-polymer interaction. Results: Spherical agglomerates were generated with uniform dispersion of drug within the matrix of polymer having size in the range of 100-500 µm. Due to spherical shape, agglomerates showed excellent flow, packability, compatibility, and mechanical properties. Good mechanical strength was indicated through higher crushing strength of agglomerates. Improved compressibility of agglomerates was indicated by lower σ 0 value in Heckel plot analysis, higher tensile strength, and lower elastic recovery compared to pure drug crystals. Sphericity and surface smoothness of agglomerates were revealed in SEM photos. In-vitro dissolution study indicated SR of drug for prolonged period. DSC and FT-IR indicated the absence of drug-polymer interaction and no change in molecular structure of drug due to agglomeration in the presence of polymers. Conclusion: Quasiemulsion solvent diffusion technique has been successfully utilized for the development of directly compressible SR spherical agglomerates of poorly soluble drugs like tiaprofenic acid.