Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides (inulin 1.8?kDa, 4?kDa and 6.5?kDa). Solid dispersions with various drug loads were prepared by lyophilization. It was found that the drug solubility in aqueous PVP solutions was significantly increased indicating the presence of drug-carrier interaction while the drug solubility was not affected by the saccharides indicating absence of drug-carrier interaction. X-ray powder diffraction and modulated differential scanning calorimetry revealed that all solid dispersions were fully amorphous. Dissolution behavior of solid dispersion tablets based on either the PVPs or saccharides was governed by both dissolution of the carrier and drug load. It was shown that a fast drug dissolution of solid dispersions with a high drug load could be obtained with carrier that showed interaction with the drug.     

Formulation Development and Dissolution Rate Enhancement of Efavirenz by Solid Dispersion Systems

The aim of this study was to enhance the dissolution rate of efavirenz using solid dispersion systems (binary and ternary). A comparison between solvent and fusion method was also investigated. Solid dispersions of efavirenz were prepared using polyethylene glycol 8000, polyvinylpyrrolidone K30 alone and combination of both. Tween 80 was incorporated to obtain a ternary solid dispersion system. Dissolution tests were conducted and evaluated on the basis of cumulative percentage drug release and dissolution efficiency. Physicochemical characterizations of the solid dispersions were carried out using differential scanning calorimetric, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Dissolution was remarkably improved in both systems compared to pure efavirenz (P<0.05). An optimum ratio was identified at a drug:polymer of 1:10. Incorporation of Tween 80 to 1:10 formulations formed using solvent method showed further improvement in the dissolution rate. Physicochemical characterization results suggested that efavirenz existed in the amorphous form in all the solid dispersion systems providing evidence of improvement in dissolution. No statistically significant difference (P>0.05) in dissolution was observed between the two methods. Binary and ternary solid dispersion systems both have showed a significant improvement in the dissolution rate of efavirenz. Formulations with only polyvinylpyrrolidone K30 showed best dissolution profile and 1:10 was identified as an optimum drug-polymer weight ratio.     

酮洛芬-聚乙烯吡咯烷酮固体分散物的制备及其体外溶出度的研究

目的提高难溶性药物酮洛芬体外溶出速度。方法以聚乙烯吡咯烷酮(PVPK30)为载体,制备药物与载体不同比例的固体分散物及物理混合物,采用X射线衍射和红外吸收方法,比较二者及药物的结晶形态,并进行体外药物溶出度的测定。结果固体分散物体外溶出速率明显高于物理混合物及酮洛芬原料的体外溶出速度,且随载体比例增加而增大。固体分散物的X射线衍射及红外吸收图谱确定了酮洛芬以无定形态分散在载体中,放置6个月后,固体分散物X射线衍射图谱没有明显变化。结论药物与载体以合适比例制备的固体分散物可以明显提高药物体外溶出速度。     

Physicochemical Characterization and Dissolution Study of Solid Dispersions of Lovastatin with Polyethylene Glycol 4000 and Polyvinylpyrrolidone K30

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to‐carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile of Lovastatin compared with tablets containing Lovastatin without PEG or PVP.     

Physicochemical characterization and dissolution study of solid dispersions of Lovastatin with polyethylene glycol 4000 and polyvinylpyrrolidone K30

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to-carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile Lovastatin compared with tablets containing Lovastatin without PEG or PVP.     

Characteristics of Rofecoxib-Polyethylene Glycol 4000 Solid Dispersions and Tablets Based on Solid Dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion–based rofecoxib tablets by the direct compression method. Solid dispersion–based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion–based oral tablets.     

Solution Behavior of PVP-VA and HPMC-AS-Based Amorphous Solid Dispersions and Their Bioavailability Implications

Purpose

To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS.

Methods

Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissolution kinetics of spray-dried dispersions were studied under sink and non-sink conditions. BMS-A supersaturation was studied in the presence of pre-dissolved PVP-VA and HPMC-AS. Potency and crystallinity of undissolved solid dispersions were determined by HPLC and DSC. Polymer dissolution kinetics were obtained by mass balance calculation. Bioavailability of solid dispersions was assessed in dogs.

Results

In solid state, both polymers are miscible with BMS-A, while PVP-VA solublizes the drug better. BMS-A dissolves similarly from both solid dispersions in vitro regardless of dissolution method, while the HPMC-AS dispersion performed much better in vivo. At the same concentration, HPMC-AS is more effective in prolonging BMS-A supersaturation; this effect was negated by the slow dissolution rate of HPMC-AS. Further study revealed that fast PVP-VA dissolution resulted in elevated drug loading in undissolved dispersions and facilitated drug recrystallization before complete release. In contrast, the hydrophobicity and slower HPMC-AS dissolution prevented BMS-A recrystallization within the HPMC-AS matrix for >24?h.

Conclusions

The lower bioavailability of PVP-VA dispersion was attributed to BMS-A recrystallization within the undissolved dispersion, due to hydrophilicity and fast PVP-VA dissolution rate. Polymer selection for solid dispersion development has significant impact on in vivo performance besides physical stability.     

Surface-active derivative of inulin (Inutec® SP1) is a superior carrier for solid dispersions with a high drug load

The aim of this study was to compare the applicability of inulin, its surface-active derivative (Inutec? SP1), and polyvinylpyrrolidone (PVP) as carriers in high drug load solid dispersions (SDs) for improving the dissolution rate of a range of lipophilic drugs (diazepam, fenofibrate, ritonavir, and efavirenz). The SDs were prepared by spray freeze-drying. Scanning electron microscopy showed that the obtained samples were highly porous spherical particles. Modulated differential scanning calorimetry showed that the drugs incorporated in these carriers were fully or partially amorphous. The solubility of the drugs in solutions of the different carriers was increased in an order: inulin 2.3 kDa < PVP K30 ? Inutec? SP1. The dissolution behavior of SD tablets was evaluated. Inutec? SP1-based SD tablets showed the best performance followed by PVP- and inulin-based SD tablets. The superior dissolution behavior of the drugs from Inutec? SP1-based SDs could be ascribed to its surface-active nature. In addition, Inutec? SP1-based SD tablets gave good physical stability at 20 °C/45% relative humidity (RH) and 40 °C/75% RH for 3 months.     

Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion-based rofecoxib tablets by the direct compression method. Solid dispersion-based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion-based oral tablets.     

托伐普坦固体分散体的制备及体外溶出特性考察

目的 采用固体分散技术提高难溶性药物托伐普坦的体外溶出度。方法 选用聚维酮K_29/32为载体材料,以溶剂蒸发法制备托伐普坦固体分散体。采用差示扫描量热法(DSC)、X-射线粉末衍射法(XRPD)对所得固体分散体进行鉴定, 并进行溶解度、体外溶出实验。结果 固体分散体的DSC 图谱及X-射线粉末衍射确定了托伐普坦以无定形态分散在载体中, 体外溶解实验表明其溶出较原料药、物理混合物均有明显提高。结论 将托伐普坦与PVP K_29/32制成固体分散体,其分散状态发生了改变,溶出性能明显提高。     

Dissolution, stability, and absorption characteristics of dicumarol in polyethylene glycol 4000 solid dispersions

The dissolution characteristics of dicumarol were markedly enhanced by preparing dispersions of drug in polyethylene glycol 4000. Solid dispersions of varying weight fractions were formed by a melt method without measurable drug degradation or evaporation. There were no significant differences in dissolution rates among weight fractions, with dynamic solubilities being approximately 2.5 times greater than dicumarol's equilibrium solubility. No indications of drug polymer complexation were noted from equilibrium or in situ absorption experiments. Incorporation of solid dispersions into direct compression tablets provided dosage forms with fast-release properties relative to test tablets of physical mixtures and a commercially available product. Percentages dissolved in 30 min were 370% greater for 1:3 and 1:5 (w/w) solid dispersion tablets compared to a commercial tablet at 37 degrees with a pH 7.5 dissolution buffer. X-ray diffraction of test powder revealed that the crystalline nature of the drug had altered during fusion preparation. Dissolution traits and drug stability for solid dispersions were maintained over 1 year of storage.     

Development and Evaluation of Melt-in-Mouth Tablets of Metoclopramide Hydrochloride Using Novel Co-processed Superdisintegrants

In the present investigation, a novel multifunctional co-processed superdisintegrants consisting of crospovidone and Kyron T-314 were fabricated by solvent evaporation method to develop melt-in-mouth tablets of metoclopramide hydrochloride with a view to enhance patient compliance by direct compression method. The simple physical blends and co-processed mixture of superdisintegrants were characterized for angle of repose, bulk density, tapped density, Carr''s index, Hausner''s ratio and compatibility studies by FTIR spectroscopy. Melt-in-mouth tablets of metoclopramide hydrochloride were prepared using the physical blends and co-processed mixture of superdisinterants and were evaluated for hardness, friability, in vitro disintegration time, in vitro dispersion time, wetting time, water absorption ratio, drug content, in vitro drug release and accelerated stability study at 40±2° temperature and 75±5% relative humidity. Among the tablets evaluated, formulation F-X prepared by adding co-processed superdisintegrants in ratio of 1:1 showed minimum in vitro dispersion time of 9.71±0.021 s, in vitro disintegration time of 5.70±0.117 s and higher amount of drug release of 99.695±0.29% at the end of 1 min. Formulation F-X was emerged as the overall best formulation based on drug release characteristics in pH 6.8 phosphate buffer compared with the tablets obtained from conventional method of manufacture as well as with marketed preparation. Analysis of drug release data indicated that formulation F-X followed first order kinetics. This study revealed that the co-processed mixture of superdisintegrants have excellent flow properties, high compressibility, render low disintegration time to tablets and have better binding properties as compared to physical blends of superdisintegrants. These materials can be a good substitute for inert superdisintegrants, which are normally used in tablet manufacturing.     

Meloxicam-Paracetamol Binary Solid Dispersion Systems with Enhanced Solubility and Dissolution Rate:Preparation,Characterization, and In Vivo Evaluation

The aim of this work included the improvement of meloxicam solubility and maximizing its pharmacological activity by forming binary solid dispersions with paracetamol. Different binary solid dispersions were prepared using paracetamol as a pharmacologically related coformer with favorable structural, dissolution, and solubility properties. The prepared binary solid dispersions were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Saturation solubility and dissolution rate were determined for meloxicam-paracetamol binary solid dispersions and compared to each drug individually. The pharmacological effects of meloxicam were enhanced in binary solid dispersions compared to the physical mixture using mice as animal models. This finding could be attributed to the improvement of meloxicam saturation solubility in the binary solid dispersion systems. Solid state characterization demonstrated the formation of amorphous phase with low crystallinity as obtained by XRD data. The solid dispersion prepared by freeze drying at 1:10 molar ratio showed more than sevenfold increase in solubility of meloxicam and more than 65% increase in dissolution rate compared to both generic preparation and physical mixture tablets. Significant differences (P < 0.05) in the analgesic effect represented by the increase in time of licking of forepaws to 7.92 s for the solid dispersion (SD) (F4) system compared to 6.15 and 4.82 s, for physical mixture and control groups were observed, respectively. A significant difference (P < 0.05) in the anti-inflammatory effect was demonstrated for the binary solid dispersion showing more than 50% decrease in the volume of carrageenan-induced tail edema compared to that of the physical mixture. Therefore, the freeze dried binary solid dispersion of meloxicam and paracetamol has shown to increase the analgesic and anti-inflammatory activities as compared to the physical mixture.     

Fast disintegrating tablets of nisoldipine for intra-oral administration

Abstract

Nisoldipine is a calcium channel blocker with low and variable oral bioavailability. This was attributed to slow dissolution and presystemic metabolism. Accordingly, the objective of this work was to enhance the dissolution rate of nisoldipine to formulate fast disintegrating tablets with rapid dissolution. Binary solid dispersions (SD) were prepared for the drug with hydroxypropyl methyl cellulose E5 (HPMC), polyvinylpyrrolidone (PVP), Pluronic F68 or polyethylene glycol 6000 (PEG 6000). SD formation increased the dissolution rate compared to pure drug with the corresponding physical mixtures failing to provide the same dissolution enhancement. This indicates that the SD enhanced dissolution is not due to the solubilizing effect of the polymer and can be due to physical change in the drug crystal which was confirmed by thermal analysis. SD with HPMC and PVP were selected for preparation of fast disintegrating tablets as they liberated most of the drug in the first 5?min. HPMC-based tablets disintegrated rapidly and released most of the drug in the first 2?min which correlated with the corresponding SD. In contrast, PVP-based tablets disintegrated slowly with gradual dissolution. This can be attributed to the binding effect of PVP. The study developed fast disintegrating tablet for intra-oral administration.     

Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution: pros and cons

The solid dispersions with poloxamer 188 (P188) and solid solutions with polyvinylpyrrolidone K30 (PVPK30) were evaluated and compared in an effort to improve aqueous solubility and bioavailability of a model hydrophobic drug. All preparations were characterized by differential scanning calorimetry, powder X-ray diffraction, intrinsic dissolution rates, and contact angle measurements. Accelerated stability studies also were conducted to determine the effects of aging on the stability of various formulations. The selected solid dispersion and solid solution formulations were further evaluated in beagle dogs for in vivo testing. Solid dispersions were characterized to show that the drug retains its crystallinity and forms a two-phase system. Solid solutions were characterized to be an amorphous monophasic system with transition of crystalline drug to amorphous state. The evaluation of the intrinsic dissolution rates of various preparations indicated that the solid solutions have higher initial dissolution rates compared with solid dispersions. However, after storage at accelerated conditions, the dissolution rates of solid solutions were lower due to partial reversion to crystalline form. The drug in solid dispersion showed better bioavailability in comparison to solid solution. Therefore, considering physical stability and in vivo study results, the solid dispersion was the most suitable choice to improve dissolution rates and hence the bioavailability of the poorly water soluble drug.     

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.     

Fundamental aspects of solid dispersion technology for poorly soluble drugs

The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug–polymer two-component system, the drug–polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.KEY WORDS: Solid dispersion, Poorly soluble drug, Phase separation, Drug–polymer interaction     

Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

To improve solubility of tadalafil (Td), a poorly soluble drug substance (3 μg/ml) belonging to the II class of the Biopharmaceutical Classification System, its six different solid dispersions (1:1, w/w) in the following polymers: HPMC, MC, PVP, PVP-VA, Kollicoat IR and Soluplus were successfully produced by freeze-drying. Scanning electron microscopy showed a morphological structure of solid dispersions typical of lyophilisates. Apparent solubility and intrinsic dissolution rate studies revealed the greatest, a 16-fold, increase in drug solubility (50 μg/ml) and a significant, 20-fold, dissolution rate enhancement for the Td/PVP-VA solid dispersion in comparison with crystalline Td. However, the longest duration of the supersaturation state in water (27 μg/ml) over 24 h was observed for the Td solid dispersion in HPMC. The improved dissolution of Td from Td/PVP-VA was confirmed in the standard dissolution test of capsules filled with solid dispersions. Powder X-ray diffraction and thermal analysis showed the amorphous nature of these binary systems and indicated the existence of dispersion at the molecular level and its supersaturated character, respectively. Nevertheless, as evidenced by film casting, the greatest ability to dissolve Td in polymer was determined for PVP-VA. The crystallization tendency of Td dispersed in Kollicoat IR could be explained by the low T_g (113 °C) of the solid dispersion and the highest difference in Hansen solubility parameters (6.8 MPa^0.5) between Td and the polymer, although this relationship was not satisfied for the partially crystalline dispersion in PVP. Similarly, no correlation was found between the strength of hydrogen bonds investigated using infrared spectroscopy and the physical stability of solid dispersions or the level of supersaturation in aqueous solution.     

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.