Dissolution Properties of Glibenclamide in Combinations with Polyvinylpyrrolidone

Abstract

Investigations were done on the enhanced aqueous solubility of glibenclamide. Eight kin & of glibenclamide coprecipitates, using two kinds of polyvinylpyrrolidone (PVP) having different molecular weights, were prepared in a solid powdered form by the conventional evaporation method. The formation of coprecipitates was confirmed by powder x-ray diffractometry, differential scanning calorimetry and Fourier-transform infrared spectroscopy. The aqueous solubility of glibenclamide was improved by increasing the concentrations of PVP. The coprecipitates prepared in this study were found to have higher dissolution rates compared to intact glibenclamide and physical mixtures of glibenclamide and PVP.     

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.     

Effect of Different Grades of Polyvinylpyrrolidone on Dissolution Rate of Chlorpropamide and its Absorption Through Rat Stomach

Coprecipitates of chlorpropamide and PVP 10000, 44000 and 700000 were prepared. Dissolution rate studies have shown that coprecipitate of Chlorpropamide and PVP 44000 (1:3.33) is by far the best combination. The same findings were also observed when all the three different coprecipitates were subjected to drug absorption studies through rat stomach. This increase in dissolution rate could be due to complex formation between the drug and the PVP irrespective of molecular weight, this was confirmed by T.L.C. and IR studies. It was also observed that the effect of PVP on increase in dissolution of insoluble drug reaches up to a certain molecular weight of PVP and decreases with further increase in molecular weight.     

The Preparation and Stability of Fast Release Furosemide – PVP Solid Dispersion

Abstract

Furosemide-PVP solid dispersion systems were prepared by co-evaporation and freeze-drying methods. The X-ray diffraction patterns indicated that furosemide in the coprecipitates was in amorphous form. The dissolution rate of furosemide was markedly increased in these solid dispersion systems. The increase in dissolution was a function of the ratio of drug to PVP used. With 1:7 ratio the best result was obtained. The 49000 mol. wt. PVP yielded the most rapid furosemide dissolution. Dissolution studies have shown that coprecipitate of furosemide-PVP (1:7) is the best combination. Factors contributing to the enhancement of furosemide' dissolution from the dispersion in PVP were discussed. The increase in release rates was attributed to the increased wettability, coacervate formation and the complexation.

The effect of aging on furosemide-PVP solid dispersions has been investigated. After storage, under the different humidities (55%, 70% and 85% RH) coprecipitates showed no change in either dissolution rate or X-ray diffraction patterns.     

Effect of Different Grades of Polyvinylpyrrolidone on Dissolution Rate of Chlorpropamide and its Absorption Through Rat Stomach

Abstract

Coprecipitates of chlorpropamide and PVP 10000, 44000 and 700000 were prepared. Dissolution rate studies have shown that coprecipitate of Chlorpropamide and PVP 44000 (1:3.33) is by far the best combination. The same findings were also observed when all the three different coprecipitates were subjected to drug absorption studies through rat stomach. This increase in dissolution rate could be due to complex formation between the drug and the PVP irrespective of molecular weight, this was confirmed by T.L.C. and IR studies. It was also observed that the effect of PVP on increase in dissolution of insoluble drug reaches up to a certain molecular weight of PVP and decreases with further increase in molecular weight.     

Preparation and Properties of Tablets Prepared from Furosemide-PVP Solid Dispersion Systems

Abstract

Tablets were prepared from the solid dispersion of furosemide: PVP by using different techniques such as direct compression and double compression. The results were compared with similar tablets prepared by physical mixture. Direct compression was much prefered, as it provided tablets with acceptable mechanical and physical qualities. On the other hand, the choice of disintegrant is very important in the formulation of furosemide: PVP solid dispersed tablets. With Kollidon CL, the best result was obtained. Disintegration mechanism of this system was also discussed. The other effective factor is the particle sizes of coprecipitates. Fine particle exhibited compression difficulty. The drug release from these tablets was 17 times greater than that from tablets prepared from physical mixture.     

Increasing the aqueous solubility of acetaminophen in the presence of polyvinylpyrrolidone and investigation of the mechanisms involved

It was shown that the aqueous solubility of acetaminophen in the presence of polyvinylpyrrolidone (PVP) increased. The solubility at 25°C increased from 14.3 mg mL^-1 in the absence of PVP, to 19.7 mg mL^-1 in the presence of 4% w/v PVP, and to 26.7 mg mL^-1 in the presence of 8% w/v PVP. Dialysis studies indicated that there is a potential of binding between PVP and acetaminophen in their aqueous solutions. Dialysis studies also revealed that the nature of interaction between PVP and acetaminophen is physical and reversible, and there was no strong binding between PVP and acetaminophen in their solutions. Infrared spectroscopy of acetaminophen/PVP solid dispersion indicated that the mechanism of interaction between PVP and acetaminophen is via hydrogen bonding. Therefore, the increase in solubility of acetaminophen in the presence of PVP is probably attributed to its ability to form a water-soluble complex with PVP.     

Supercritical Antisolvent Versus Coevaporation— Preparation and Characterization of Solid Dispersions

The objective of this work was to improve the dissolution rate and aqueous solubility of oxeglitazar. Solid dispersions of oxeglitazar in PVP K17 (polyvinilpyrrolidone) and poloxamer 407 (polyoxyethylene-polyoxypropylene block copolymer) were prepared by supercritical antisolvent (SAS) and coevaporation (CoE) methods. Drug-carrier formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography, UV/VIS spectroscopy and in vitro dissolution tests. The highest dissolution rate (nearly 3-fold higher than raw drug) was achieved by preparation of drug/PVP K17 coevaporate. Oxeglitazar/PVP K17 solid dispersions were stabilized by hydrogen bonding but contained higher amount of residual dichloromethane (DCM) than poloxamer 407 formulations regardless of the method of preparation. SAS prepared oxeglitazar/poloxamer 407 dissolved more than two times faster than raw drug. However, unlike PVP K17, poloxamer 407 did not form a single phase amorphous solid solution with oxeglitazar which has been manifested in higher degrees of crystallinity, too. Among the two techniques, evaluated in this work, conventional coevaporation resulted in higher amorphous content but SAS reduced residual solvent content more efficiently.     

Supercritical antisolvent versus coevaporation: preparation and characterization of solid dispersions

The objective of this work was to improve the dissolution rate and aqueous solubility of oxeglitazar. Solid dispersions of oxeglitazar in PVP K17 (polyvinilpyrrolidone) and poloxamer 407 (polyoxyethylene-polyoxypropylene block copolymer) were prepared by supercritical antisolvent (SAS) and coevaporation (CoE) methods. Drug-carrier formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography, UV/VIS spectroscopy and in vitro dissolution tests. The highest dissolution rate (nearly 3-fold higher than raw drug) was achieved by preparation of drug/PVP K17 coevaporate. Oxeglitazar/PVP K17 solid dispersions were stabilized by hydrogen bonding but contained higher amount of residual dichloromethane (DCM) than poloxamer 407 formulations regardless of the method of preparation. SAS prepared oxeglitazar/poloxamer 407 dissolved more than two times faster than raw drug. However, unlike PVP K17, poloxamer 407 did not form a single phase amorphous solid solution with oxeglitazar which has been manifested in higher degrees of crystallinity, too. Among the two techniques, evaluated in this work, conventional coevaporation resulted in higher amorphous content but SAS reduced residual solvent content more efficiently.     

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.     

Characterization and evaluation of tenoxicam coprecipitates

Tenoxicam is a nonsteroidal anti-inflammatory drug belonging to the oxicam group. The drug is slightly soluble in water. In a trial to increase its dissolution, different commonly used excipients were selected to prepare coprecipitates with tenoxicam. The coprecipitates were prepared using the solvent evaporation method, and the ratio used was 1:3 drug to additive. The prepared coprecipitates were subjected to a dissolution study, and they were characterized using infrared (IR) and differential scanning calorimetry (DSC) techniques. Dissolution profiles of most of the prepared coprecipitates demonstrated higher dissolution than pure tenoxicam. The characteristic peaks of tenoxicam in the IR spectrum disappeared in the spectra of all the prepared coprecipitates except those prepared with sodium chloride, for which the IR spectrum was identical to that of the pure drug. The characteristic peaks of tenoxicam disappeared in the DSC thermograms of the coprecipitates under study, indicating a change in structure from pure tenoxicam. Characterization of the coprecipitates by IR and DSC techniques revealed structural changes in the prepared coprecipitates from the plain drug, which may account for increased dissolution rates.     

Characterization and Evaluation of Tenoxicam Coprecipitates

Tenoxicam is a nonsteroidal anti-inflammatory drug belonging to the oxicam group. The drug is slightly soluble in water. In a trial to increase its dissolution, different commonly used excipients were selected to prepare coprecipitates with tenoxicam. The coprecipitates were prepared using the solvent evaporation method, and the ratio used was 1:3 drug to additive. The prepared coprecipitates were subjected to a dissolution study, and they were characterized using infrared (IR) and differential scanning calorimetry (DSC) techniques. Dissolution profiles of most of the prepared coprecipitates demonstrated higher dissolution than pure tenoxicam. The characteristic peaks of tenoxicam in the IR spectrum disappeared in the spectra of all the prepared coprecipitates except those prepared with sodium chloride, for which the IR spectrum was identical to that of the pure drug. The characteristic peaks of tenoxicam disappeared in the DSC thermograms of the coprecipitates under study, indicating a change in structure from pure tenoxicam. Characterization of the coprecipitates by IR and DSC techniques revealed structural changes in the prepared coprecipitates from the plain drug, which may account for increased dissolution rates.     

Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems

Context: Piperine alkaloid, an important constituent of black pepper, exhibits numerous therapeutic properties, whereas its usage as a drug is limited due to its poor solubility in aqueous medium, which leads to poor bioavailability.

Objective: Herein, a new method has been developed to improve the solubility of this drug based on the development of solid dispersions with improved dissolution rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG) and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of piperine and carriers were also prepared for comparison.

Methods: The physicochemical properties of the prepared solid dispersions were examined using SEM, TEM, DSC, XRD and FT-IR. In vitro dissolution profile of the solid dispersions was recorded and compared with that of the pure piperine and physical mixtures. The effect of these carriers on the aqueous solubility of piperine has been investigated.

Results: The solid dispersions of piperine with Sor, PEG and PVP exhibited superior performance for the dissolution of piperine with a drug release of 70%, 76% and 89%, respectively after 2?h compared to physical mixtures and pure piperine, which could be due to its transformation from crystalline to amorphous form as well as the attachment of hydrophilic carriers to the surface of poorly water-soluble piperine.

Conclusion: Results suggest that the piperine solid dispersions prepared with improved in vitro release exhibit potential advantage in delivering poorly water-soluble piperine as an oral supplement.     

Gefitinib–cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies

Background: Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs). Methods: Phase solubility studies of gefitinib with hydroxypropyl βCD (HPβCD) and randomly methylated βCD (RMβCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC). Results: Gefitinib formed stable complexes with HPβCD and RMβCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M^?1 for HPβCD and RMβCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an A_N type of phase-solubility diagrams, whereas gefitinib and HPβCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in A_P-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPβCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC. Conclusion: Gefitinib formed stable inclusion complexes with HPβCD and RMβCD, and the solubility and dissolution rate of the drug was significantly increased.     

A Study of the Complexation Between Danazol and Hydrophilic Cyclodextrin Derivatives

Abstract

Complexation between danazol, a steroid used for endometriosis, and both hydroxypropyl- β-cyclodextrin (HPCD) and sulfobutyl ether-β-cyclodextrin (SBE) was studied in solution and solid state. Complexation was evaluated in solution using solubility studies and proton magnetic resonance (¹H NMR) spectroscopy, and in the solid state using x-ray diffraction, Fourier-transform infrared spectroscopy (FTIR)), and dissolution studies. Solubility studies suggested the existence of a 1:1 complex between danazol and either HPCD or SBE. ¹H NMR showed that complexation occurs by inclusion of the isoxazole ring of danazol into the cyclodextrin cavity in both cases. Powder x-ray diffraction indicated that danazol existed in a crystalline noncomplexed form at low danazol-to-cyclodextrin ratios in the coprecipitates prepared by solvent evaporation method, while at higher ratios danazol existed in an amorphous complexed form. This ratio was 1:10 w/w for HPCD and 1:20 for SBE; the higher ratio in the case of SBE is attributed to early precipitation of danazol from the solvent used for preparation. FTIR studies showed that the complexation was accompanied by a shift of the O-H stretching of danatol hydroxyl group to a higher frequency, which is attributed to the disruption of the intermolecular hydrogen bonding. The dissolution rate of danazol from HPCD coprecipitates was higher than crystalline danazol in aqueous-isopropanolic medium, while SBE coprecipitates showed reduced dissolution rates due to the low solubility of SBE in isopropanol. However, SBE coprecipitates showed higher dissolution rates in water than in the isopropanolic medium.     

Development of solid dispersions of β-lapachone in PEG and PVP by solvent evaporation method

β-lapachone (βlap) has shown potential use in various medical applications. However, its poor solubility has limited its systemic administration and clinical applications. The aim of this work is to develop solid dispersions of βlap using poly (ethylene glycol) (PEG 6000) and polyvinylpyrrolidone (PVP K30) as hydrophilic polymers and evaluate the dissolution rate in aqueous medium. Solid dispersions were prepared by solvent evaporation method using different weight ratios of βlap and hydrophilic polymer (1:1, 1:2, and 1:3). Characterization performed by differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy showed that βlap was molecularly dispersed within the polymer matrix. The in vitro dissolution tests showed an enhancement in the dissolution profile of βlap as solid dispersions prepared in both PVP and PEG, although the former showed better results. The drug:polymer ratio influenced βlap dissolution rate, as higher amounts of hydrophilic polymer led to enhanced drug dissolution. Thus, this study demonstrated that solid dispersions of βlap in PVP offers an effective way to overcome the poor dissolution of βlap.     

A Study of the Complexation Between Danazol and Hydrophilic Cyclodextrin Derivatives

Complexation between danazol, a steroid used for endometriosis, and both hydroxypropyl- β-cyclodextrin (HPCD) and sulfobutyl ether-β-cyclodextrin (SBE) was studied in solution and solid state. Complexation was evaluated in solution using solubility studies and proton magnetic resonance (¹H NMR) spectroscopy, and in the solid state using x-ray diffraction, Fourier-transform infrared spectroscopy (FTIR)), and dissolution studies. Solubility studies suggested the existence of a 1:1 complex between danazol and either HPCD or SBE. ¹H NMR showed that complexation occurs by inclusion of the isoxazole ring of danazol into the cyclodextrin cavity in both cases. Powder x-ray diffraction indicated that danazol existed in a crystalline noncomplexed form at low danazol-to-cyclodextrin ratios in the coprecipitates prepared by solvent evaporation method, while at higher ratios danazol existed in an amorphous complexed form. This ratio was 1:10 w/w for HPCD and 1:20 for SBE; the higher ratio in the case of SBE is attributed to early precipitation of danazol from the solvent used for preparation. FTIR studies showed that the complexation was accompanied by a shift of the O-H stretching of danatol hydroxyl group to a higher frequency, which is attributed to the disruption of the intermolecular hydrogen bonding. The dissolution rate of danazol from HPCD coprecipitates was higher than crystalline danazol in aqueous-isopropanolic medium, while SBE coprecipitates showed reduced dissolution rates due to the low solubility of SBE in isopropanol. However, SBE coprecipitates showed higher dissolution rates in water than in the isopropanolic medium.     

Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate

Solid dispersion systems have been widely used to enhance dissolution rate and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scale-up present a number of difficulties which has greatly limited their commercial applications. In this study, solid dispersions (SDs) of desloratadine (DSL) with povidone (PVP) and crospovidone (cPVP) were prepared by spray coating technique. The process involved the spray application of 96% ethanol solution of DSL and PVP/cPVP, and subsequent deposition of the coprecipitates onto microcrystalline cellulose pellets during drying by air flow in a mini spray coater. The results from the present study demonstrated that the spray coating process is efficient in preparing SDs with enhanced drug dissolution rate and it is highly efficient in organic solvent removal. Both PVP and cPVP greatly improved drug dissolution rate by SDs, with PVP showing better solubilization capability. Very fast drug dissolution rate is achieved from SDs containing PVP regardless of differences in K grade. SD with smaller particles of cPVP have higher drug dissolution rate in comparison to the cPVP with larger particles. Results from physical state characterization indicate that DSL in SDs exist in the amorphous (high free-energy) state which is probably stabilized by PVP/cPVP. After 6-month accelerated stability study, DSL remains amorphous, while PVP and cPVP act as anti-plasticizing agents, offering efficient steric hindrance for nucleation and crystal growth.     

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.