Enhanced Dissolution of Ibuprofen Using Solid Dispersion with Polyethylene Glycol 20000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility and in vitro drug release. Loss of individual surface properties during melting and re-solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting toward the lower melting temperature of the drug peak in SDs in DSC study indicated the possibilities of drug–polymer interactions. FTIR spectra showed the presence of drug crystalline in SDs. The effect of improved dissolution on the oral absorption of ibuprofen in rats was also studied. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C_max, and a significant decrease in T_max over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low-temperature melting method using polyethylene glycol 20000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution, and absorption rate of ibuprofen.     

Formation of Amorphous Telmisartan Polymeric Microparticles for Improvement of Physicochemical Characteristics

In order to improve solubility and dissolution rate of poorly aqueous soluble telmisartan, its amorphous polymeric microparticles with PVP K30 were prepared with or without aid of adsorbent (Aerosil200/Sylysia350) using spray-drying technique. The pure drug and formulations were evaluated for their morphology, particle size, aqueous solubility, and in vitro drug release. Solid state characterization of pure drug and microparticles was carried out by Fourier transform infrared spectroscopy (FTIR), x-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). FTIR indicated hydrogen bonding interaction with an absence of any other chemical interaction between drug and excipient. The results of DSC and XRPD revealed transformation of crystalline drug to amorphous form which was confirmed by SEM. Significant solubility and dissolution enhancement was observed for all polymeric microparticles over pure drug and spray-dried pure drug. This enhancement was attributed to the wetting effect of polymers, altered surface morphology with micronization and decreased crystallinity of drug particles.     

Enhancement of dissolution rate of valdecoxib using solid dispersions with polyethylene glycol 4000

The aim of the present study was to enhance the dissolution rate of valdecoxib using its solid dispersions (SDs) with polyethylene glycol (PEG) 4000. The phase solubility behavior of valdecoxib in the presence of various concentrations of PEG 4000 in water was obtained at 37°C. The solubility of valdecoxib increased with increasing amount of PEG 4000 in water. Gibbs free energy (ΔG°_tr) values were all negative, indicating the spontaneous nature of valdecoxib solubilization, and they decreased with increase in the PEG 4000 concentration, demonstrating that the reaction conditions became more favorable as the concentration of PEG 4000 increased. The SDs of valdecoxib with PEG 4000 were prepared at 1:1, 1:2, 1:5, and 1:10 (valdecoxib: PEG 4000) ratio by melting method. Evaluation of the properties of the SDs was performed by using dissolution, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) studies. The SDs of valdecoxib with PEG 4000 exhibited enhanced dissolution rate of valdecoxib, and the rate increased with increasing concentration of PEG 4000 in SDs. Mean dissolution time (MDT) of valdecoxib decreased significantly after preparation of SDs and physical mixture with PEG 4000. The FTIR spectroscopic studies showed the stability of valdecoxib and absence of well-defined valdecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of valdecoxib in SDs of valdecoxib with PEG 4000. The SEM pictures showed the formation of effective SDs of valdecoxib with PEG 4000, since well-defined changes in the surface nature of valdecoxib, SDs, and physical mixture were observed.     

Incorporation of paclitaxel solid dispersions with poloxamer188 or polyethylene glycol to tune drug release from poly(ϵ-caprolactone) films

Here we report the application of solid dispersion (SD) technique to improve paclitaxel (PTX) release from poly(?-caprolactone) (PCL)-based film. Paclitaxel solid dispersions (SDs) with either poloxamer188 (PXM) or polyethylene glycol (PEG) were successfully prepared by a melting method and then incorporated into PCL films, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and In vitro drug release/dissolution studies. It was found that PTX was faster released from the SDs than the corresponding physical mixtures (PMs) or PTX alone. For the PCL films with almost the same PTX loading, drug release from films containing SDs was remarkably faster than that from the film directly incorporated with PTX particles, and the films containing SDs with PXM exhibited a faster drug release than those with PEG. An increase In the content of PXM had no significant influence on PTX release from the films containing SDs. Incorporation of a higher content of SDs led to slower drug release from PCL films, indicating that PTX loading had a dominating effect on drug release. Through this study, we demonstrated the feasibility of the application of SD technique on the improvement of PTX release from PCL films and offered some beneficial information on modulating drug release behavior by changing the compositions and contents of the SDs-loaded PCL films.     

Solid carriers for improved solubility of glipizide in osmotically controlled oral drug delivery system

The purpose of this study was to increase the solubility of glipizide (gli) by solid dispersions SDs technique with polyvinylpyrrolidone (PVP) in aqueous media. The gli-PVP solid dispersion systems was prepared by physical mixing or spray drying method, and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transformation-infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The elementary osmotic pumps (EOPs) were prepared with gli-PVP complex and the effect of the PVP percentages on the enhancing of gli dissolution rate was studied. The influences of various parameters e.g., drug- PVP ratio, level of solubility modifier, coating weight gain and diameter of drug releasing orifice on drug release profiles were also investigated. The solubility and dissolution rates of gli were significantly increased by solid dispersion using spray dried method as well as their physical mixture. The obtained results indicated that gli-PVP solid dispersion system has suitable solubility behavior in EOP tablets.     

Solid Carriers for Improved Solubility of Glipizide in Osmotically Controlled Oral Drug Delivery System

The purpose of this study was to increase the solubility of glipizide (gli) by solid dispersions SDs technique with polyvinylpyrrolidone (PVP) in aqueous media. The gli–PVP solid dispersion systems was prepared by physical mixing or spray drying method, and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transformation-infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The elementary osmotic pumps (EOPs) were prepared with gli–PVP complex and the effect of the PVP percentages on the enhancing of gli dissolution rate was studied. The influences of various parameters e.g., drug- PVP ratio, level of solubility modifier, coating weight gain and diameter of drug releasing orifice on drug release profiles were also investigated. The solubility and dissolution rates of gli were significantly increased by solid dispersion using spray dried method as well as their physical mixture. The obtained results indicated that gli–PVP solid dispersion system has suitable solubility behavior in EOP tablets.     

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers,in vitro dissolution,antioxidant potential and in vivo anti-platelet effect

This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O–H???O?=?C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.     

Cyclodextrin nanosponges to enhance the dissolution profile of quercetin by inclusion complex formation

ABSTRACT

The therapeutic potential of quercetin is mostly hampered by its low water solubility and poor absorption. The aim of this study was to enhance the dissolution rate of quercetin by molecular encapsulation with cyclodextrin nanosponges. The inclusion complexes were obtained by freeze-drying method. Inclusion complexes were characterized by Fourier Transformed Infrared Spectroscopy (FTIR), x-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), transmission electron microscopy (TEM), and dissolution testing. FTIR, XRD, and DSC studies confirmed the interactions of quercetin with nanosponges. TEM images revealed the spherical morphology of complexes. The dissolution of the drug nanosponge complex was significantly higher compared with the pure drug in simulated intestinal fluid (SIF; pH 6.8). The results indicated that the degree of cross-linking has the significant influence on dissolution. Nanosponges with lower degree of cross-linking released 91% of the drug within 45 min, whereas nanosponges with higher degree of cross-linking resulted in sustained release up to 24 h.     

The Dissolution and Complexing Properties of Ibuprofen and Ketoprofen when Mixed with N-Methylglucamine

The objectives of this study were to improve the aqueous dissolution properties of the poorly soluble nonsteroidal anti-inflammatory drugs ibuprofen and ketoprofen and to explore the use of N-methylglucamine (meglumine) to enhance the dissolution properties of poorly water-soluble drug powders. Changes in both differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) results indicate that possibly complexes were produced between ibuprofen and N-methylglucamine. Similar changes were not observed for equivalent ketoprofen and N-methylglucamine mixtures. The results of solubility and dissolution studies in water at 25°C and 37°C showed that N-methylglucamine, in mixtures and coprecipitates, increased the solubility, intrinsic dissolution, and powder dissolution of ketoprofen and ibuprofen. N-Methylglucamine significantly improved the solubility and dissolution properties of both ibuprofen and ketoprofen even when DSC and XRD behavior did not indicate the formation of complexes.     

Studies on the in vitro Release of Ibuprofen from Polyethylene Glycol-Polyvinyl Acetate Mixtures Liquid Filled into Hard Gelatin Capsules

The release of ibuprofen from mixtures of polyethylene glycol (PEG) with polyvinyl acetate (PVAc) has been studied in vitro and complemented by x-ray diffraction measurements, differential scanning calorimetry (DSC), and melting point determinations via hot-stage microscopy (HSM). Results indicate that ibuprofen release can be affected markedly by alteration of the PVAc concentration. The molecular weight of the PEG and the pH of the dissolution medium are also shown to affect the release profile. Visual observation during the drug release process revealed a complex behavior which included emission of liquidlike droplets, formation of a crust around the releasing mass, and/or production of flakes of solid material. This behavior appeared to have a disadvantageous effect on the reproducibility of drug release. Construction of a phase diagram from results of thermal analysis using DSC and HSM indicated the formation of an eutectic mixture with a composition of 35% ibuprofen and 65% PEG 1500 and a melting point of 36°C. The complex behavior of the drug-releasing mass is discussed in terms of this phase diagram. Only the release data for systems containing 4% w/w or more of PVAc could be linearized by plotting against the square root of time whereas data for all of the systems studied could be linearized by first-order plots.     

Effect of semicrystalline copolymers in solid dispersions of pioglitazone hydrochloride: in vitro-in vivo correlation

Objective: The study was aimed to improve the dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water-soluble drug.

Significance: Poor aqueous solubility of PGH was overcome by the design of SDs. Level A correlation demonstrated between in vitro release and bioavailability of PGH, suggest its biowaiver potential.

Methods: The effects of semicrystalline copolymers (poloxamer 407 and gelucire 50/13) and methods of preparations on dissolution behavior, in vivo performance, and stability of PGH SDs were investigated. All the SDs were characterized by FTIR, TGA, DSC, XRD, and SEM.

Results: FTIR and TGA showed the compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns & SEM indicated a change from a crystalline to an amorphous state. Gelucire 50/13 was observed to have greater ability to form SDs than poloxamer 407 in solvent evaporation method (SM). Prevention of recrystallization during storage suggested stability of the formulation. Gelucire 50/13 based SD, prepared by SM remarkably increased the dissolution within 15?min (87.27?±?2.25%) and was supported by dissolution parameters (Q₁₅, IDR, RDR, % DE, f₁, f₂). These SDs showed pH-dependent solubility. In vivo test showed significantly (p?<?.05) higher AUC_0–t and C_max, which were about 3.17 and 4.34 times that of the pure drug respectively.

Conclusion: Gelucire 50/13 was found to be a suitable carrier for SM for preparation of SDs of PGH as evident from increased dissolution and bioavailability.     

Development of a novel starch-derived porous silica monolith for enhancing the dissolution rate of poorly water soluble drug

A novel starch-derived porous silica monolith (PSM) and porous starch foam (PSF) were developed as a carrier in order to improve the dissolution of lovastatin. PSM was prepared by the starch gel template method and PSF was prepared by the solvent exchange method. The morphology and structure of PSM and PSF were characterized by scanning electron microscopy (SEM) and nitrogen adsorption/desorption analysis. Lovastatin was loaded into PSM and PSF by immersion/solvent evaporation. Nano-pore spatial confinement effect on the drug dissolution was systematically studied by SEM, Fourier transform infrared spectroscopy (FTIR), thermogravametric analysis (TGA), x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and in-vitro drug dissolution studies. Lovastatin adsorbed in PSM was amorphous and lovastatin absorbed on PSF was partially present as microcrystal in the pores of PSF and partially in crystalline form distributed on the surface of PSF. PSM and PSF allowed immediate release of lovastatin and enhanced the dissolution rate. These results provide important information about the mechanism of drug adsorption and release. Accordingly, PSM and PSF have a promising future as a vehicle for the oral delivery of poorly water soluble drugs. Moreover, the effect of PSM is better than that of PSF.     

Melt dispersion granules: formulation and evaluation to improve oral delivery of poorly soluble drugs – a case study with valsartan

Solid dispersion (SD) technique is a promising strategy to improve the solubility and dissolution of BCS class II drugs. However, only few products are marketed till today based on SD technology due to poor flow properties and stability. The present work was intended to solve these problems by using combination approach, melt dispersion and surface adsorption technologies. The main aim of the present work is to improve the absorption in the stomach (at lower pH) where the absorption window exists for the drug by improving the dissolution, resulting in the enhancement of oral bioavailability of poorly soluble, weakly acidic drug with pH dependant solubility, i.e. valsartan. Melt dispersion granules were prepared in different ratios using different carriers (Gelucire 50/13, PEG 8000 and Pluronic F-68) and lactose as an adsorbent. Similarly, physical mixtures were also prepared at corresponding ratios. The prepared dispersion granules and physical mixtures were characterized by FTIR, DSC and in vitro dissolution studies. DSC studies revealed reduction in the crystallinity with a possibility of presence of amorphous character of drug in the dispersion granules. From dissolution studies, valsartan Gelucire dispersion (GSD4; 1:4 ratio) showed complete drug release in 30?min against the plain drug which showed only 11.31% of drug release in 30?min. Pharmacokinetic studies of optimized formulation in male Wistar rats showed 2.65-fold higher bioavailability and 1.47-fold higher C_max compared to pure drug. The melt dispersion technology has the potential to improve dissolution and the bioavailability of BCS class II drugs.     

Physicochemical characterization of interaction of ibuprofen by solid-state milling with aluminum hydroxide

This present study is a preliminary exploration of the affinity between a carboxylic model drug ibuprofen and aluminum hydroxide. Ibuprofen was comilled with aluminum hydroxide in different weight ratios in the solid state and was characterized by scanning electron microscopy (SEM), X-ray powder diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. XRD and SEM studies indicated complete interaction of ibuprofen with aluminum hydroxide and complete amorphization of aluminum hydroxide-ibuprofen complexed salt as well, on comilling with aluminum hydroxide at 1:2 ratio. FTIR data showed the disappearance of acid carbonyl peak with the appearance and the corresponding increase in absorbance of new signal at 1,682 cm(-1) in the 1:1 and 1:2 ibuprofen-aluminum hydroxide-comilled powder. The accompanied increase in the absorbance of carboxylate peak in the ibuprofen-aluminum hydroxide physical mixture, and 1:0.1, 1:0.5, 1:1, and 1:2 (IBA(pm), and IB(1)A(0.1), IB(1)A(0.5), IB(1)A(1), and IB(1)A(2), respectively) comilled powder indicated an acid-base reaction between ibuprofen and aluminum hydroxide. On storage at 40 degrees C and 75% relative humidity (RH) for 10 weeks, XRD study showed the absence of reversion to the crystalline state and FTIR data revealed continued increase of new signal at 1,682 cm(-1) relative to carboxylic acid peak and no reappearance of carboxylic acid peak. In vitro dissolution studies revealed that the percent release of ibuprofen from the aluminum hydroxide-comilled powder is in the following order: IB(1)A(2) < IB(1)A(1) < ibuprofen crystal < ibuprofen milled alone < IB(1)A(0.1) < IB(1)A(0.5). Aluminum metal cation might have interacted to form a complex through the carboxyl and carbonyl groups of ibuprofen. Improved dissolution of drug associated with IB(1)A(0.1) and IB(1)A(0.5) is because of the absence of a new signal at 1,682 cm(-1) and improved amorphization of the drug to some extent. Dissolution of drug affected in IB(1)A(2) and IB(1)A(1) may be because of the insoluble stable complex formation.     

Enhancement of the dissolution and permeation rates of meloxicam by formation of its freeze-dried solid dispersions in polyvinylpyrrolidone K-30

Freeze-drying (FD) and solvent evaporation (SE) were used to prepare solid dispersions (SDs) of meloxicam (MX) in polyvinylpyrrolidone K-30 (PVP). The SDs were prepared at different ratios, namely 1:1, 1:3, and 1:5 MX:PVP weight ratio. Differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), and x-ray powder diffractometry (XPD) were utilized to characterize the physicochemical properties of the SDs. Meloxicam (MX) in the solid dispersions appeared with less crystallinity form and was present in a complete amorphous form at higher PVP ratio. Dissolution rates of MX as a pure drug, physical mixtures (PMs), and SDs indicated a marked increase of the dissolution rate of MX in presence of PVP. The increase in the dissolution rate was dependent on the ratio of PVP and the method of preparation. In addition, the permeability of the drug through standard cellophane membrane and hairless mouse skin was also evaluated. The permeation rate of MX was significantly increased in the case of SDs and was dependent on the ratio of PVP. The results were primarily due to increase wettability, the solubilization of the drug by the carrier, and formation of MX amorphous form.     

In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier

In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.     

Study of a novel disintegrable oleanolic acid-polyvinylpolypyrrolidone solid dispersion

Novel solid dispersions of oleanolic acid-polyvinylpolypyrrolidone (OLA-PVPP SDs) were designed and prepared to improve the apparent solubility of drug, as well as to improve the stability, fluidity and compressibility of SDs. Disintegrable OLA-PVPP SDs were then evaluated both in vitro and in vivo. DSC, XRD, IR and SEM analysis proved the formation of OLA-PVPP SD and its amorphous state. The results of fluidity study, moisture absorption test and stability test showed that OLA-PVPP SD with good fluidity and qualified stability was successfully obtained. Meanwhile excellent dissolution rate was achieved for in vitro studies; dissolution test showed that ～50–75% of OLA was dissolved from SDs within the first 10?min, which is about 10–15 times of free OLA. In vivo study indicated that the formation of solid dispersion could largely improve the absorption of OLA, resulting in a much shorter T_max (p?C_max (p?0→∞ of OLA-PVPP SDs (1:6) were 155.4?±?37.24?h·ng/mL compared to the 103.11?±?26.69?h·ng/mL and 94.92?±?13.05?h·ng/mL of OLA-PVPP physical mixture (1:6) and free OLA, respectively. These proved PVPP could be a promising carrier of solid dispersions and was industrially feasible alternative carrier in the manufacture of solid dispersions.     

In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier

In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.     

Development of novel core-shell dual-mesoporous silica nanoparticles for the production of high bioavailable controlled-release fenofibrate tablets

Novel core-shell dual-mesoporous silica nanoparticles (DMSN) were successfully prepared as a carrier in order to improve the dissolution of fenofibrate and obtain an oral highly bioavailable controlled-release drug delivery system using the osmotic pump technology. Fenofibrate was loaded into DMSN by an adsorption method. The solid state properties of fenofibrate in DMSN, before and after drug loading, were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption analysis (BET), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro release tests showed that DMSN increased the dissolution rate of fenofibrate and produced zero-order release in push–pull osmotic pump tablets (OPT). The relative bioavailability of OPT was 186.9% in comparison with the commercial reference product. In summary, osmotic pump technology in combination with solid dispersion technology involving nanometer materials is a promising way for achieving the oral delivery of poorly water-soluble drugs.     

Enhancement of the Dissolution and Permeation Rates of Meloxicam by Formation of Its Freeze-dried Solid Dispersions in Polyvinylpyrrolidone K-30

ABSTRACT

Freeze-drying (FD) and solvent evaporation (SE) were used to prepare solid dispersions (SDs) of meloxicam (MX) in polyvinylpyrrolidone K-30 (PVP). The SDs were prepared at different ratios, namely 1:1, 1:3, and 1:5 MX:PVP weight ratio. Differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), and x-ray powder diffractometry (XPD) were utilized to characterize the physicochemical properties of the SDs. Meloxicam (MX) in the solid dispersions appeared with less crystallinity form and was present in a complete amorphous form at higher PVP ratio. Dissolution rates of MX as a pure drug, physical mixtures (PMs), and SDs indicated a marked increase of the dissolution rate of MX in presence of PVP. The increase in the dissolution rate was dependent on the ratio of PVP and the method of preparation. In addition, the permeability of the drug through standard cellophane membrane and hairless mouse skin was also evaluated. The permeation rate of MX was significantly increased in the case of SDs and was dependent on the ratio of PVP. The results were primarily due to increase wettability, the solubilization of the drug by the carrier, and formation of MX amorphous form.