对乙酰氨基酚-β-环糊精包合物和固体分散体的研究

目的:本文采用研磨法制备了对乙酰氨基酚-β-环糊精（β－ＣＤ）包合物,熔融法制备了其固体分散体。方法：建立了对酰氨基酚包合物及其固体分散体外溶出度测定方法。结果：对乙酰氨基酚包合物（１：１Ｗ／Ｗ）（Ａ）和ＰＥＧ６０００固体分散体（１：２Ｗ／Ｗ）（Ｂ）的体外溶出参数Ｋｒ、Ｔ(５０)、Ｔｄ分别（Ａ）：０．８３３ｍｉｎ（-１）、３．９ｍｉｎ和４．４ｍｉｎ;（Ｂ）：０．５０６ｍｉｎ（-１）、４．４ｍｉｎ和５．１ｍｉｎ。结论：经t检验,对乙酰氨基酚包合物及固体分散体与胶囊剂之间的Ｔ(５０)、Ｔｄ均有极显著性差异（Ｐ＜０．０１）。     

Inclusion complexes of tadalafil with natural and chemically modified β-cyclodextrins. I: Preparation and in-vitro evaluation

The aim of this work was to investigate the inclusion complexation between tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5), and two chemically modified β-cyclodextrins: hydroxypropyl-β-cyclodextrin (HP-β-CD) and heptakis-[2,6-di-O-methyl]-β-cyclodextrin (DM-β-CD), in comparison with the natural β-cyclodextrin (β-CD) in order to improve the solubility and the dissolution rate of the drug in an attempt to enhance its bioavailability. Inclusion complexation was investigated in both the solution and the solid state. The UV spectral shift method indicated guest–host complex formation between tadalafil and the three cyclodextrins (CDs). The phase solubility profiles with all the used CDs were classified as A_p-type, indicating the formation of higher order complexes. The complexation efficiency values (CE), which reflect the solubilizing power of the CDs towards the drug, could be arranged in the following order: DM-β-CD > HP-β-CD > β-CD. Solid binary systems of tadalafil with CDs were prepared by kneading and freeze-drying techniques at molar ratios of 1:1, 1:3 and 1:5 (drug to CD). Physical mixtures were prepared in the same molar ratios for comparison. Physicochemical characterization of the prepared systems at molar ratio of 1:5 was studied using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and Fourier-transform infrared spectroscopy (FTIR). The results showed the formation of true inclusion complexes between the drug and both HP-β-CD and DM-β-CD using the freeze-drying method at molar ratio of 1:5. In contrast, crystalline drug was detectable in all other products. The dissolution of tadalafil from all the prepared binary systems was carried out to determine the most appropriate CD type, molar ratio, and preparation technique to prepare inclusion complexes to be used in the development of tablet formulation for oral delivery of tadalafil. The dissolution enhancement was increased on increasing the CD proportion in all the prepared systems. Both the CD type and the preparation technique played an important role in the performance of the system. Irrespective of the preparation technique, the systems prepared using HP-β-CD and DM-β-CD yielded better performance than the corresponding ones prepared using β-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the β-CD derivatives.     

Simultaneous enantioseparation of antiparkinsonian medication Rotigotine and related chiral impurities by capillary zone electrophoresis using dual cyclodextrin system

A dual cyclodextrin (CD) system consisting of sulfated β-CD (S-β-CD) and methyl-β-CD (M-β-CD) modified capillary zone electrophoresis (CZE) method was proposed to separate the antiparkinsonian drug Rotigotine ((−)-(S)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin) and related chiral impurities (2-(N-propylamino)-5-hydroxytetralin, 2-(N-propylamino)-5-methoxytetralin). The method was optimized by varying the CD type, the buffer pH, individual CD concentration of the dual system and the ionic strength of background electrolyte. Under the optimum conditions, i.e. 2% (w/v) S-β-CD and 2% (w/v) M-β-CD in 100 mM sodium phosphate (pH 2.5) as the running buffer, separation voltage −20 kV, detected at 200 nm and temperature controlled at 20 °C, a satisfactory separation of the six analytes was accomplished. The optimized method was validated for specificity, precision, linearity, accuracy and stability using sodium benzenesulfonate as the internal standard. The relative standard deviation for migration time was less than 0.58%, and 3.78% for peak area ratio. The linearity ranged from 0.005 to 0.25 mM. The recovery ranged from 95.9% to 108.3%. The limits of detection and limits of quantification for each enantiomer were 0.003 and 0.01 mM, respectively. This method was utilized for evaluating the chiral purity of five batches of Rotigotine.     

Chiral separation of methoxamine and lobeline in capillary zone electrophoresis using ethylbenzene-deactivated fused-silica capillary columns and cyclodextrins as buffer additives

The complete chiral separation of methoxamine and lobeline was achieved by capillary zone electrophoresis on an ethylbenzene-deactivated fused-silica capillary column and with cyclodextrins (CDs) as buffer additives. Among the CDs investigated in this study, i.e. -CD, β-CD, dimethyl-β-CD, hydroxypropyl-β-CD and γ-CD, all the three β-type CDs showed chiral recognition on the two drugs investigated. Under the investigated conditions, the baseline chiral separation of methoxamine can be achieved with 90 mM Tris–H₃PO₄ (pH 2.5) containing 11.5 mM of the three β-type CDs, with dimethyl-β-CD giving the best resolution, whereas the baseline chiral separation of lobeline can be realized by using 90 mM Tris–H₃PO₄ buffer (pH 2.5) containing 5.8 mM dimethyl-β-CD or 29.5 mM hydroxypropyl-β-CD.     

Effects of β-cyclodextrins on skin: implications for the transdermal delivery of piribedil and a novel cognition enhancing-drug, S-9977

The effects of β-cyclodextrin (β-CD), randomly methylated β-cyclodextrin (RAMEB) and 2-hydroxypropyl β-cyclodextrin (HPβ-CD) on skin were investigated. The three cyclodextrins (CDs) were able to destabilize model liposomes and to extract significant amounts of cholesterol from isolated stratum corneum (SC). However, only RAMEB extracted all the major lipid classes from isolated SC, as shown by thin layer chromatography. Both RAMEB and HPβ-CD could release 5–10% of the extractable cholesterol as well as proteins from hairless rat skin. Nevertheless, CDs did not induce any major modification of the differential scanning calorimetry (DSC) profile or the Fourier-transformed infrared (FTIR) spectrum of SC. This was explained by the low percutaneous penetration of CDs. Furthermore, the influence of RAMEB on the transdermal diffusion through hairless rat skin of piribedil, a central dopaminergic agonist and of S-9977, a novel cognition enhancing drug, was studied. RAMEB was found to decrease the transdermal flux of piribedil, with which it forms an inclusion complex, as shown by NMR. Conversely, RAMEB increased by 2-fold the percutaneous absorption of the S-9977 hydrochloride, which does not interact with CD. Finally, a combination of oleic acid and RAMEB greatly increased by about 30-fold the flux of S-9977 hydrochloride.     

Investigations into the structure and composition of β-cyclodextrin/poly(acrylic acid) microspheres

Microspheres composed of the hydrophilic polymer poly(acrylic acid) (PAA), with and without β-cyclodextrin (β-CD), were prepared by a water-in-oil (w/o) solvent evaporation technique. Microspheres were characterised for particle size, β-CD and residual oil content. The type of matrix formed during microsphere synthesis was investigated by solid state carbon ¹³C NMR, in vitro release of β-CD and swelling measurements. A high encapsulation efficiency of the β-CD was observed (>90%). The in vitro release of β-CD in water over 24 h was initially rapid (≈70% in 3 h) with no further loss thereafter, suggesting potential covalent binding of the residual β-CD. NMR indicated that in the presence of β-CD, two concomitant chemical processes occur during microsphere synthesis: (i) esterification of the hydroxyl group(s) of the β-CD with the carboxylic acid groups of the PAA; and (ii) the formation of intra-/inter-polymer acid anhydrides.     

Physicochemical characterization of solid dispersions of the antiviral agent UC-781 with polyethylene glycol 6000 and Gelucire 44/14

The purpose of this study was to prepare and characterize solid dispersions of the antiviral thiocarboxanilide UC-781 with PEG 6000 and Gelucire 44/14 with the intention of improving its dissolution properties. The solid dispersions were prepared by the fusion method. Evaluation of the properties of the dispersions was performed using dissolution studies, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffraction. To investigate the possible formation of solid solutions of the drug in the carriers, the lattice spacings [d] of PEG 6000 and Gelucire 44/14 were determined in different concentrations of UC-781. The results obtained showed that the rate of dissolution of UC-781 was considerably improved when formulated in solid dispersions with PEG 6000 and Gelucire 44/14 as compared to pure UC-781. From the phase diagrams of PEG 6000 and Gelucire 44/14 it could be noted that up to approximately 25% w/w of the drug was dissolved in the liquid phase in the case of PEG 6000 and Gelucire 44/14. The data from the X-ray diffraction showed that the drug was still detectable in the solid state below a concentration of 5% w/w in the presence of PEG 6000 and Gelucire 44/14, while no significant changes in the lattice spacings of PEG 6000 or Gelucire 44/14 were observed. Therefore, the possibility of UC-781 to form solid solutions with the carriers under investigation was ruled out. The results from infrared spectroscopy together with those from X-ray diffraction and differential scanning calorimetry showed the absence of well-defined drug–polymer interactions.     

The properties of solid dispersions of indomethacin or phenylbutazone in polyethylene glycol

The effects of molecular weight of polyethylene glyeols (PEGs) on the dissolution rates and crystallinity of its solid dispersions with indoniethacin and phenylbutazone have been examined. The dissolution rates of both solid-dispersed drugs decreased as the molecular weight of PEG increased. The indoniethacin dissolution profiles were essentially linear using constant surface area disc methodology and a limiting dissolution rate of about 10.6 mg · min⁻¹ was observed. The phenylbutazone dissolution profiles were. however, generally linear-curvic usually giving lower release rates than the comparative indomethacin weight fractions. A limiting dissolution rate for the linear portions of the profiles was about 1.8 mg · min⁻¹. Infra-red spectra indicated that the differences between the two drugs could partly be explained on the basis of PEG crystallinity. Generally bands in the ranges 1100–1130 and 1200–1400 cm⁻¹ were poorly differentiated in indomethacin dispersions (PEG 1500, PEG 4000 and PEG 6000) but were better differentiated in phenylbutazone dispersions (PEG 4000, PEG 6000 and PEG 20,000). A greater proportion of amorphousness within the PEG moiety was predicted in indomethacin dispersions by the appearance of a new weak band at 1326 cm⁻¹ and by a decrease in intensity of the band at 845 cm⁻¹ at the expense of the peak at 960 cm⁻¹. The evidence was supported by differential scanning calorimetry. The heats of fusion were 44.7, 46.4, 47.2 and 39.5 cal · g⁻¹ for PEG 1500, PEG 4000, PEG 6000 and PEG 20.000 respectively. Heats of fusion for indomethacin dispersions (2, 5 and 10% drug) were generally lower than for the corresponding values for phenylbutazone dispersions-with the exception of PEG 20,000 dispersions. For example, values were obtained of 30.6 and 37.9 cal · g⁻¹ for PEG 1500 dispersions containing 10% indomethacin and phenylbutazone, respectively.     

Enhancement of solubility and permeability of Candesartan cilexetil by using different pharmaceutical interventions

The poor solubility and wettability of Candesartan cilexetil (CAN) leads to poor dissolution and hence, low bioavailability after oral administration. The aim of the present study was to improve the solubility and dissolution rate and hence the permeability of CAN by preparing solid dispersions/inclusion complexes. Solid dispersions were prepared using PEG 6000 [hydrophilic polymer] and Gelucire 50/13 [amphiphilic surfactant] by melt agglomeration (MA) and solvent evaporation (SE) methods in different drug-to-carrier ratios, while inclusion complexes were made with hydroxypropyl-β-cyclodextrin (HP-β-CD) [complexing agent] by grinding and spray drying method. Saturation solubility method was used to evaluate the effect of various carriers on aqueous solubility of CAN. Based on the saturation solubility data, two drug-carrier combinations, PEG 6000 (MA 1:5) and HP-β-CD (1:1 M grinding) were selected as optimized formulations. FTIR, DSC, and XRD studies indicated no interaction of the drug with the carriers and provided valuable insight on the possible reasons for enhanced solubility. Dissolution studies showed an increase in drug dissolution of about 22 fold over the pure drug for PEG 6000 (MA 1:5) and 12 fold for HP-β-CD (1:1 M grinding). Ex-vivo permeability studies revealed that the formulation having the greatest dissolution also had the best absorption through the chick ileum. Capsules containing solid dispersion/ complex exhibited better dissolution profile than the marketed product. Thus, the solid dispersion/inclusion complexation technique can be successfully used for enhancement of solubility and permeability of CAN.     

A comparison of two formulations of intradermal capsaicin as models of neuropathic pain in healthy volunteers

AIMS

To compare the dose–response relationships of two formulations [Tween- or hydroxypropyl-β-cyclodextrin (HP-β-CD)-based] of intradermal capsaicin in healthy volunteers and to assess the effect of potential covariates of response. One, 10, 30 and 100 µg in 10 ml were compared for the outcomes of flare, spontaneous pain, mechanical allodynia and hyperalgesia in eight healthy men and eight healthy women.

RESULTS

The formulations produced comparable responses at doses 1, 10 and 30 µg, but in all parameters the response was less at 100 µg with the Tween formulation. Mean area for hyperalgesia was 9 cm²[95% confidence interval (CI) 5, 13] higher with the HP-β-CD formulation. Flare area was 5 cm² (95% CI 8, 13) greater with the HP-β-CD formulation. There was a significant difference between pain responses from the injection site on the upper forearm compared with the lower forearm on all four pain assessments. In contrast, significant differences were seen in pain response between nondominant and dominant arm for flare, allodynia and hyperalgesia but not for spontaneous pain. A significant difference in sex was seen only for hyperalgesia. The nominal 100-µg dose of the Tween formulation contained only 39% of label strength in the aqueous phase, which may explain the lower pharmacodynamic response.

CONCLUSION

The formulations are comparable over the dose range 1–30 µg. The significantly lower pain response at the 100 µg dose in the Tween compared with the HP-β-CD formulation is likely to be due to limitations in solubility at the 100 µg level. Given the greater ease of formulation and the superior dose–response relationship, the HP-β-CD formulation is preferable for use in the model in future studies.     

Improvement of the dissolution kinetics of SR 33557 by means of solid dispersions containing PEG 6000

Solid dispersions of SR 33557 in preparations containing from 30 to 80% w/w polyethylene glycol 6000 (PEG 6000) were prepared by the fusion method. The solubility of the drug substance either alone or in solid dispersions was determined in pH 1.2 and 4.5 media (extraction fluid NFXII, without enzyme). A large increase in the solubility was noted from the 80% w/w PEG preparation. A wettability study performed by measuring the contact angle on tablets of either drug substance or PEG 6000, or solid dispersions, revealed a minimal contact angle for the 80% w/w PEG 6000 solid dispersion (eutectic composition of SR 33557/PEG 6000 phase diagram). Dissolution kinetic analysis performed at pH 1.2 on all solid dispersions, on the physical mixtures containing 70 and 80% w/w PEG 6000, and on SR 33557 alone, showed a maximum release rate (100%) for the solid dispersions containing 70 and 80% w/w PEG 6000. The dissolution rate of the physical mixtures was faster than that of the drug substance alone but remained, however, lower than that of the solid dispersions, at the same composition. It was also observed that the dissolution rate, at pH 1.2 and 4.5, of the 70% w/w PEG 6000 solid dispersion was practically pH independent, which was not the case for the drug substance alone. The latter solid dispersion showed a slowing down of the dissolution kinetics after 3 months storage at 50°C whereas no change in the dissolution rate was observed following storage for 12 months at 25°C.     

Characterization of ternary solid dispersions of Itraconazole in polyethylene glycol 6000/polyvidone-vinylacetate 64 blends.

The good compatibility between Itraconazole and polyvidone-vinylacetate 64 (PVPVA 64) was pointed out previously. However, the dissolution properties of these systems left room for improvement. Therefore polyethylene glycol 6000 (PEG 6000), known for its solubilizing and wetting properties, was added to the PVPVA 64 matrix. Physicochemical analysis showed that up to 10% of PEG 6000 could be mixed with PVPVA 64. Addition of 10%, 20% or 40% of Itraconazole rendered amorphous solid dispersions consisting of a ternary mixed phase and a PVPVA 64 rich amorphous phase. If the PEG 6000 fraction was elevated up to 25% of the carrier, the PEG 6000 crystallinity degree was around 73+/-0.6%. Up to 20% of Itraconazole could be molecularly dispersed in the 25/75 w/w polymer blend. An Itraconazole melting peak could be detected for the sample containing 40% of drug. Dissolution experiments showed that no benefit was obtained by adding PEG 6000 to the PVPVA 64 matrix for samples containing up to 20% of Itraconazole. The dissolution of the ternary dispersions with 40% of Itraconazole on the other hand showed improvement compared to binary Itraconazole/PVPVA 64 dispersions.     

Phase solubility behavior of hydrophilic polymer/cyclodextrin/lansoprazole ternary system studied at high polymer concentration and by response surface methodology

Evaluation of polymer/cyclodextrin (CD)/drug ternary systems has been performed at low polymer levels to date, and the cross-interaction of polymers and CDs has not been well studied. In this study, the effects of PVP K30 and PEG 6000 on the complexation ability of β-CD and 2-hydroxypropyl-β-cyclodextrin (HPCD) with lansoprazole (LSP) was investigated. The phase solubility of polymer/CD/LSP ternary systems was first studied at polymer levels of 0%, 2% and 6%, respectively. A response surface methodology was then employed to investigate the cross-interaction of polymers/CDs on phase solubility at polymer levels up to 10%. Results indicated A_L-type inclusion for both β-CD and HPCD. Increase in PEG concentration leads to improved complexation efficiency, whereas increase of PVP lead to decreased CE, which is attributable to the strong interaction between PVP and LSP. Second-order polynomial equations were well employed to estimate the relationship between LSP solubility and the two independent variables. The response surface showed that PVP and PEG had no significant effects on LSP/CD complexation, while a synergistic effect on LSP solubility was observed at higher concentrations of HPCD and PEG. It is concluded that high levels of polymer lead to increased LSP solubility but not significant increase in CE.     

布格呋喃固体分散体的体外研究

布格呋喃(buagafuran,AF-5)是以( )香芹酮为起始原料通过立体选择性合成的沉香呋喃类化合物[1].它具有显著的抗焦虑作用,毒副作用低,市场前景广阔.布格呋喃为油状液体,脂溶性强,不溶于水.用植物油稀释进行小鼠灌胃,抗焦虑活性与空白组比较无统计学意义,不能较好地发挥药效.室温放置易发生降解,化学稳定性差.这些缺     

Phase solubility behavior of hydrophilic polymer/cyclodextrin/lansoprazole ternary system studied at high polymer concentration and by response surface methodology

Evaluation of polymer/cyclodextrin (CD)/drug ternary systems has been performed at low polymer levels to date, and the cross-interaction of polymers and CDs has not been well studied. In this study, the effects of PVP K30 and PEG 6000 on the complexation ability of β-CD and 2-hydroxypropyl-β-cyclodextrin (HPCD) with lansoprazole (LSP) was investigated. The phase solubility of polymer/CD/LSP ternary systems was first studied at polymer levels of 0%, 2% and 6%, respectively. A response surface methodology was then employed to investigate the cross-interaction of polymers/CDs on phase solubility at polymer levels up to 10%. Results indicated A(L)-type inclusion for both β-CD and HPCD. Increase in PEG concentration leads to improved complexation efficiency, whereas increase of PVP lead to decreased CE, which is attributable to the strong interaction between PVP and LSP. Second-order polynomial equations were well employed to estimate the relationship between LSP solubility and the two independent variables. The response surface showed that PVP and PEG had no significant effects on LSP/CD complexation, while a synergistic effect on LSP solubility was observed at higher concentrations of HPCD and PEG. It is concluded that high levels of polymer lead to increased LSP solubility but not significant increase in CE.     

Characterization of ternary solid dispersions of itraconazole, PEG 6000, and HPMC 2910 E5

In order to reduce the crystallinity of PEG 6000, blends were prepared by spray drying and extrusion with the following polymers; PVP K25, PVPVA 64, and HPMC 2910 E5. The maximal reduction of crystallinity in PEG 6000 was obtained by co-spray drying with HPMC 2910 E5. In the next step the model drug Itraconazole was added to the blend and the resulting ternary solid dispersions were characterized. The results of this study show that the addition of PEG 6000 to the Itraconazole/HPMC 2910 E5 system leads to phase separation that in most cases gives rise to recrystallization of either PEG 6000 or Itraconazole. For all ternary dispersions containing 20% of Itraconazole the drug was highly amorphous and the dissolution was improved compared to the binary 20/80 w/w Itraconazole/HPMC 2910 E5 solid dispersion. For all ternary dispersions containing 40% of Itraconazole, the drug was partially crystalline and the dissolution was lower than the dissolution of the binary 40/60 w/w Itraconazole/HPMC 2910 E5 dispersion. These results show that provided Itraconazole is highly amorphous the addition of PEG 6000 to HPMC 2910 E5 leads to an increase in drug release.     

Fast-dissolving tablets of glyburide based on ternary solid dispersions with PEG 6000 and surfactants

Marketed glyburide tablets present unsatisfying dissolution profiles that give rise to variable bioavailability. With the purpose of developing a fast-dissolving tablet formulation able to assure a complete drug dissolution, we investigated the effect of the addition to a reference tablet formulation of different types (anionic and nonionic) and amounts of hydrophilic surfactants, as well as the use of a new technique, based on ternary solid dispersions of the drug with an hydrophilic carrier (polyethylene glycol [PEG] 6000) and a surfactant. Tablets were prepared by direct compression or previous wet granulation of suitable formulations containing the drug with each surfactant or drug:PEG:surfactant ternary dispersions at different PEG:surfactant w/w ratios. The presence of surfactants significantly increased (p<0.01) the drug dissolution rate, but complete drug dissolution was never achieved. On the contrary, in all cases tablets containing ternary solid dispersions achieved 100% dissolved drug within 60 min. The best product was the 10:80:10 w/w ternary dispersion with PEG 6000 and sodium laurylsulphate, showing a dissolution efficiency 5.5-fold greater than the reference tablet formulation and 100% drug dissolution after only 20 min.     

Similarities in the release rates of different drugs from polyethylene glycol 6000 solid dispersions

The dissolution rates (mg min-1) of 10 drugs, solid dispersed by fusion in polyethylene glycol 6000 (PEG 6000) have been examined by rotating disc methodology. The dispersions generally displayed release rates which were linearly dependent upon the drug concentration (% drug) at high polymer content. However the range over which this linearity was encountered varied unduly, e.g. 0-2% for phenylbutazone and 0-15% for paracetamol. The slope of this line (mean value: 0.451 mg min-1 % -1) was statistically the same for nine of the drugs studied, the exception being griseofulvin which did not form a true solid dispersion but was a microcrystalline dispersion of the drug within the PEG. During fusion, chain scission of the PEG 6000 occurred in the presence of several drugs. PEG 6000 was incompatible with disulfiram, frusemide, chlorothiazide and chlorpropamide.     

Role of Cyclodextrins in Nanoparticle-Based Drug Delivery Systems

Cyclodextrins (CDs) are cyclic oligosaccharides with unique hydrophobic interior surfaces. Three parent CDs, α-CD, β-CD, and γ-CD, are further chemically modified primarily to make them suitable for parenteral administration, and these are used for many pharmaceutical applications. CDs offer distinctive advantages due to their unique ability to form inclusion complexes with a variety of organic and inorganic lipophilic molecules. This attribute is promising for a wide range of fields such as drug delivery, cancer therapy, gene delivery, and biosensing. In recent years, CDs have become more commonly used functional materials in nanoparticle (NP)-based drug delivery. The properties of NPs can be advantageously modified by the inclusion of CDs or their derivatives. CD-conjugated NPs (CD-NPs) have many benefits such as improved drug solubility and serve as drug carriers to specific locations such as cancer cells, which reduces toxicity to normal cells. In addition, CDs can overcome the limitations of NPs such as low encapsulation efficiency and drug loading. This review will discuss the various uses of CDs as it applies to NP-based drug carriers. Specifically, how CDs enhance the characteristics of polymeric, magnetic, lipid, metallic, and mesoporous NPs are discussed.     

Effect of counterions on the interactions in solid dispersions between polyethylene glycol, griseofulvin and alkali dodecyl sulphates

Solid dispersions of polyethylene glycol (PEG) 3000 and 10% w/w griseofulvin with or without different surfactants incorporated were prepared by the melting method. The anionic surfactants lithium dodecyl sulphate (LiDS), sodium dodecyl sulphate (SDS) and potassium dodecyl sulphate (KDS) were added in equivalent amounts, ˜ 2% w/w. Phase analysis was performed by X-ray powder diffraction and investigation of short-range structure by ¹³C-CP/MAS solid-state NMR. In all samples with surfactant added, solid solutions (PEG/MDS)_1−x griseofulvin_x were formed. The properties of the solid solutions with Na⁺ and K⁺ ions were almost identical. The addition of LiDS created a structure of the solid solution that was more crystalline than that structure of the sodium- and potassium-containing compounds. The ion with the highest charge-to-radius ratio, Li⁺, formed chemical bonds that were different from those of the other ions. This was indicated by a changed influence on the hydrophilic parts of the griseofulvin molecules in the lithium compound. The melting behaviour of the solid solutions, investigated by DSC, showed a second transformation in the melt at 186–196°C, indicating a two-phase region in the liquid phase. For the lithium-containing compounds the transformation appeared at lower temperature than for the sodium- and potassium-containing compounds.