Characterization Of Solid Dispersions Research Articles

Improving Oral Bioavailability of Meloxicam: Development and Characterization of Solid Dispersions

This study investigated the development of a solid dispersion to improve the solubility and dissolution of meloxicam, a poorly water-soluble drug. Meloxicam is used to treat pain and inflammation in various conditions. The challenge was to enhance the drug's oral bioavailability by overcoming its low solubility. Two approaches were explored:
 
 1. Kneading method with Poloxamer 407: This method resulted in a formulation with significantly improved solubility compared to the pure drug.
 Solvent evaporation method with PVP K-30: While this method offered satisfactory solubility enhancement, it was not as effective as the kneading method with Poloxamer 407.Following the development of the optimized solid dispersion, a suspension formulation was prepared using various suspending agents. The optimized drug formula was then incorporated into the suspension mix. Characterization studies confirmed compatibility between the drug and excipients. FT-IR analysis showed no interaction between the drug and the carriers. Scanning electron microscopy (SEM) revealed a change in meloxicam particle morphology from crystalline to a more amorphous form, indicating a reduction in particle size and a potential explanation for the improved dissolution profile. The dissolution profile of the solid dispersion suspension prepared by the kneading method with Poloxamer 407 outperformed the one prepared with the solvent evaporation method and PVP K-30.This study demonstrates the effectiveness of the kneading method with Poloxamer 407 in developing a solid dispersion of meloxicam with enhanced solubility and dissolution. The optimized formulation exhibited good stability, acceptable drug content and release, and satisfactory rheological properties. This approach has the potential to improve the bioavailability of meloxicam and lead to a more effective oral dosage form.
 
 Keywords: Oral Bioavailability, Meloxicam:, Solid Dispersions , FT-IR analysis, SEM

Solid Dispersions of Gefitinib with D-α-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl β-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells

This study focuses on the development and characterization of solid dispersions (SDs) of Gefitinib (GEF) to improve its aqueous solubility and therapeutic activity against lung cancer. SDs were prepared by the co-precipitation method with tocopheryl-polyethylene-glycol succinate-1000 (TPGS) (F1), sodium lauryl sulfate (SLS) (F2) and complexation of F1 with hydroxypropyl β-cyclodextrin (HP-β-CD) (F3). Optimal formulations (F1 and F3) were used against A549 cells to determine the apoptosis, expressions of p53 and caspases. F3 has shown the highest solubility (1271.21 µg/mL), followed by F1 (1003.69 µg/mL), F2 (707.81 µg/mL) and GEF pure (303.85 µg/mL) in 0.1N HCl. Dissolution at 1.2 pH significantly enhanced the release from F3 (99.19%), followed by F1 (94.76%), F2 (85.70%) and GEF pure (37.26%) during 120 min. Complexation of GEF–TPGS with HP-β-CD significantly improved drug release with high dissolution efficiency (78.57%) in 24.9 min of mean dissolution time. Differential scanning calorimetry revealed crystalline to amorphous conversion of GEF in SDs, which was confirmed by scanning electron microscopy. Fourier transform infrared and proton nuclear magnetic resonance spectral analysis revealed no interaction between GEF and excipients. The IC50 values were 2.239, 3.135 and 4.471 µM for F3, F1 and GEF pure, respectively, against A549 cells. Increased expressions of p53 (5.9-, 4.6- and 3.04-fold), caspase-3 (5.38-, 3.78- and 3.01-fold) and caspase-9 (5.35-, 3.76- and 2.47-fold) in the case of F3, F1 and GEF pure, respectively, as compared to the untreated A549 cells indicated improved apoptotic potential of the SDs. TPGS SDs and their complexation with HP-β-CD improved the solubility, dissolution and efficacy of GEF against A549 cells. So, they can be a suitable alternative to the conventional GEF formulations against non-small-cell lung cancers.

An Overview Onsustained Release Formulations Using Solid Dispersion as Solubility Enhancement Technique.

Biopharmaceutical classification system is important for determining the bioavailability of the drug. Drugs that dissolve slowly in water can be effectively solid-dispersed to increase their bioavailability. The bioavailability issue can be due to insufficient solubility of permeability. The poorly water-soluble medication dissolves more quickly when combined with the water-soluble carriers used to make solid dispersion. The review paper concentrates on the preparation techniques, benefits, drawbacks, and characterization of solid dispersion. Pharmaceuticals with sustained release have recently emerged as a very practical tool in medical practise, providing patients with a variety of real and perceived benefits. By minimising fluctuations in Using the therapeutic dose of the medicine in the body, sustained release is another promising reduction technique side effects. The major methods for creating tablets with a sustained release matrix are wet granulation, direct compression, or dispersion. In this review paper got the information about various polymers and different methods which are used for the formulate the sustained release tablet.

Investigating the physicochemical properties of solid dispersions based on semicrystalline carriers: A case study with ketoprofen

Hydrophilic semicrystalline carriers represent an alternative to amorphous polymers due to their low melting temperature, useful for the production of solid dispersions (SDs) by melting-based technologies. This research aims to compare SDs of ketoprofen (KET) and three different semicrystalline carriers (PEG, Poloxamer and Gelucire) regarding miscibility, phase behavior, molecular interactions and stability. KET was chosen owing to its low solubility and high glass forming ability. Estimation of drug-excipient miscibility was performed by Flory-Huggins theory. Negative Gibbs free energy indicated a spontaneous mixing of KET with the three carriers and miscibility in the order PEG > Poloxamer > Gelucire. SDs up to 40 % w/w of drug were produced by melting process at a temperature below KET melting point. Characterization of SDs was performed by differential scanning calorimetry, polarized light microscopy and powder X-ray diffraction. In case of PEG and Poloxamer, the drug incorporation did not affect carrier crystallinity, while KET was in the amorphous state. Differently, KET retarded the crystallization of Gelucire and at high drug loadings the SDs were amorphous and semisolid. FT-IR analysis revealed a strong interaction between KET and the three carriers. Finally, PEG-based SDs above 20 % KET loading displayed drug crystallization after 6 months of storage; while Poloxamer and Gelucire-based SDs showed KET crystallization only at 40 % KET. Due to its less hydrophilic character and limited water uptake, Gelucire showed the best stability among the three excipients.

A Comprehensive Review on Solid Dispersion Technique to Enhance the Solubility and Bioavailability of Poorly Water-Soluble Drugs

The majority of the time, oral administration of medications to patients is chosen. However, many medications have limited uses in oral delivery due to their low solubility. In the pharmaceutical industry, improving a drug's water solubility is a primary goal. One of the most crucial elements affecting bioavailability and dissolution rate is solubility. By using different polymers, the solid dispersion approach improves the bioavailability and dissolution rate of poorly soluble medicines. In this review, techniques for solid dispersion were examined, along with the characterization of solid dispersions.

Formulation and Physicochemical Characterization of Glibenclamide Solid Dispersion Using Various Carriers

Aims: Glibenclamide is an oral hypoglycemic agent exhibits inadequate aqueous solubility resulting in poor and unpredictable bioavailability. The study was designed to enhance the solubility and dissolution of glibenclamide by solid dispersion.
 Place and Duration of Study: Department of Pharmacy, University of Rajshahi, Bangladesh between June 2017 and July 2018.
 Methodology: Solid dispersions of glibenclamide were prepared by solvent evaporation technique using mixture of PEG-8000, sodium citrate, HPMC as additives in different ratios and subsequently, in-vitro dissolution studies were performed. The characterization of solid dispersions was done by Differential Scanning Calorimetry, Powder X-ray Diffractometer, Fourier Transform Infrared Spectroscopy and Scanning Electron Microscope.
 Results: Out of twelve formulations, the GCHP-4 composed of glibenclamide: HPMC: Na-citrate: PEG-8000 1:1:1:1) demonstrated highest percentage of yield (87.76%) and encapsulation efficiency (95.68%). The maximum dissolution of glibenclamide obtained from GCHP-4 (3.34 µg/ml), which was 5.2-fold higher than that of pure glibenclamide (0.64 µg/ml) at 120 min. The mechanism of increased solubility of glibenclamide from solid dispersion might be resulted due to the conversion of its crystalline form into amorphous state and no interaction between drug and carriers which was confirmed by differential scanning calorimetry and fourier transform infrared spectroscopy respectively.
 Conclusion: The dissolution rate of glibenclamide was greatly increased when loaded in solid dispersions which might be responsible for the improvement of its bioavailability in aqueous medium.

Bioavailability Enhancement of Ritonavir by Solid Dispersion Technique

Ritonavir is an antiretroviral agent used in the treatment of HIV-infection. It is a BCS class IV drug having poor aqueous solubility leading to poor bioavailability. Bioavailability is the amount of drug that enters the systemic circulation. The bioavailability is affected by various factors like solubility, dissolution and stability. In order to improve bioavailability, many techniques like solid dispersions, nanoparticles, liposomes, encapsulation methods were present. The main aim of this study is to improve the bioavailability of ritonavir with the help of Polyvinyl Pyrrolidone (PVP) K-30 by using solid dispersion technique. Different formulations were made with varied concentrations of polymer. Characterization of solid dispersion was done by phase solubility, drug content, Fourier transformed infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and in-vitro dissolution studies. From phase solubility studies that apparent solubility constant was found to be 42.227M-1. The drug content of the binary system of ritonavir and PVP was found to be ranging from 99.17% to 103.06%. %. FT-IR studies revealed that there was no drastic change in the wave number indicating polymer compatibility with drug. In-vitro dissolution studies proved that there was an increase in drug release of ritonavir with incremental ratios of polymer and F5 formulation has shown almost 95% of drug release.
 Keywords: Bioavailability, Solid dispersion, Polyvinyl pyrrolidine, Solvent evaporation, Dissolution.

Formulation and Optimization of Zolmitriptan Orodispersible Tablets

Zolmitriptan is a selective 5-hydroxytryptamine receptor agonist reported for the acute migraine treatment, having poor water solubility leads to poor bioavailability. In the present study, attempt to improve the bioavailability of zolmitriptan with the help of PVP K-30 using the microwave irradiation method. The zolmitriptan and PVP K- 30 in 1:1 ratio was subjected to microwave irradiation for different times such as 60,80,100,120 seconds at 650 watts. Characterization of solid dispersion was done by drug content, XRD, FTIR, DSC. FTIR analysis demonstrated there are no compatibility issues. XRD studies prove that the solid dispersion was in amorphous form. DSC studies prove that solid dispersion was amorphous based on the intensity of peaks. The prepared dispersion was made into orodispersible tablets by direct compression. The optimization of these formulations was carried out by using 32 factorial designs on Design Expert 10.0 software. In order to examine the effect of independent variables Crospovidone (X1), croscarmellose sodium (X2), and combined effect of independent variables 32 factorial design was selected. In this design, two responses such as disintegration time and % drug release were evaluated, and experimental trials are performed for all 9 formulations. For all formulations, the precompression and post-compression parameters were studied. Based upon the model optimized formulation (C1 and C2) was obtained having the disintegration time (34.4±0.84 and 39.8±0.91) and %drug release (98.7±0.42 and 93.2±0.46) respectively.
 Keywords: Zolmitriptan, Solid dispersion, Microwave irradiation, Crospovidone, Croscarmellose sodium.

Formulation and Characterization of Solid Dispersion Containing Capsaicin for the Treatment of Diabetes

Background: Chili peppers are widely used in many cuisines as a spice, and capsaicin is the main component. It has been reported that capsaicin acts as an antihyperglycemic agent. However, it shows poor aqueous solubility and bioavailability. Objective: The is to enhance the aqueous solubility and antihyperglycemic activity of capsaicin through solid dispersion formulation. Methods: Solid dispersions were prepared by the solvent evaporation method using polyethylene glycol 6000 (PEG 6000) as a hydrophilic carrier. Polymer-drug miscibility and drug crystallinity were characterized through the differential thermal analysis and X-ray powder patterns analysis. Solid dispersions were evaluated for solubility, in vitro drug dissolution and in vivo animal study in rats. Results: Results of x-ray powder patterns analysis showed a considerable reduction of drug crystallinity in solid dispersion. Differential thermal analysis result revealed a complete disappearance of capsaicin melting onset temperature in solid dispersion. From the phase solubility data, it was observed that the aqueous solubility of capsaicin was increased with increasing concentration of PEG 6000. Solid dispersion formulation showed considerable enhancement of in vitro release of drugs in comparison to pure capsaicin. In vivo animal study in rats shows that the solid dispersion containing capsaicin significantly reduced the blood glucose level in comparison to the free capsaicin. Conclusion: Higher anti-hyperglycemic effect of capsaicin loaded solid dispersion in comparison to the pure drug may be due to the enhancement of aqueous solubility of capsaicin. Thus, the solid dispersion of capsaicin showed a simple approach for capsaicin delivery with improved antidiabetic activity.

Improving Solubility of the Telmisartan that is Poorly Water Soluble by Wet Granulation and Vitrification Process

Telmisartan (TS) have developed for the treatment of hypertension as the angiotensin II receptor blocker. TS belongs to class II drug in BCS classification and it has good permeability. But, it is poorly water soluble. Biological half-life of TS is 24 hours because it has not good bioavailability (only 42∼58%). The absorption of a drug is often limited by dissolution rate. Drug dissolution is important factor to the therapeutic efficacy of a medicine. Therefore, TS requires alternative methods of drug delivery system to improve solubilization. In this study, we have prepared solid dispersions (SD) of the TS, polyvinylpyrrolidone (PVP) K-30 using rotary evaporation to promote release rate. So, we made sustained release formulation to make that is continually released and reduced the number of administration to patients. We selected the methods which are wet granulation (WG) and vitrification (VT) for sustained release. WG is a common techinique in the pharmaceutical industry that is mixing the powder to make bonds between powder particles using water. VT is techinique that transforms the crystalline particle into amorphous state using cryomilling. We measured the characterization of SD that was performed using various methods to analyze the structure of powder sample. Characterizations of SD were performed to analyze the surface by scanning electron microscopy. The crystallinity and molecular structure are analyzed by Fourier transform infrared spectroscopy, powder X-ray diffractometer. Also, thermal porperties are analyzed by differential scanning calorimeter. In vitro dissolution test assessed by RP-HPLC to analyze dissolution rate of sustained release formulation and solid dispersion. In this results, these indicate that both methods improve solubility and dissolution rate. The drug solubility of processed VT almost greater than the pure drug and WG. And, in Bats, VT 3 has higher dissolution rates than others. So, this results are useful to improve TS in the pharmaceutical industry.

RECENT APPROACHES OF SOLID DISPERSION: A NEW CONCEPT TOWARD ORAL BIOAVAILABILITY SABITRI BINDHANI* , SNEHAMAYEE MOHAPATRA

Solid dispersion (SD) has been a major advanced technology in overcoming dissolution and bioavailability problem of poorly soluble compounds. Formulation of SD in water-soluble carrier has becoming more researched over the past four decades for solubility and relative bioavailability enhancement. By reduction of the size of the drug particle to the minimum level which will enhance drug wettability and ultimately bioavailability will be definitely improved. This review article elaborates recent advanced technology and characterization of SDs and also discusses the problems and their solution for the development of better formulations.

Solid Dispersions for Oral Administration: An Overview of the Methods for their Preparation.

Oral drug delivery remains the most physiological and therefore the most preferred, simplest and easiest administration route. Nevertheless, a multitude of potentially clinically important drugs will not reach the market or achieve their full potential unless their oral bioavailability is improved by formulation. The aim of this review is to present an overview of properties, formulation, excipients and characterization of solid dispersions corresponding to one of the different formulation strategies for design and development of poorly soluble drugs. This work will review and compare in detail the evolution of solid dispersions focused on the different methods of formulation and production of solid dispersions, their stability, their release properties, their pharmacokinetics and methods for their physicochemical characterization.

Formulation, Optimization and Characterization of Solid Dispersion of Glibenclamide

Aim: The aim of the present study was to increase the solubility and dissolution of Glibenclamide. Materials and Methods: Various batches of solid dispersion of Glibenclamide using water soluble carriers such as PEG (PEG 4000 and PEG 1500), were prepared as per the design expert (8.0.5) to optimize the drug release profile using response surface methodology (Face centered central composite design). Results: DSC and FTIR were used to characterize the solid dispersions. No chemical interaction was found between Glibenclamide and polymers. F3 and F13 was found to be optimized batch according to the Face centered central composite design (FCCCD). Conclusion: Drug release was directly proportional to the concentration of polymer used for the formulation of solid dispersion. Thus, Glibenclamide with PEG 4000 and PEG 1500 had faster dissolution rate than Glibenclamide itself. Key words : Solid Dispersion, Dissolution, Physical Mixture, Polyethylene Glycol.

Preparation and characterization of solid dispersion using a novel amphiphilic copolymer to enhance dissolution and oral bioavailability of sorafenib

The objective of the current study was to enhance dissolution and oral bioavailability of the poorly water-soluble drug, sorafenib (SFN), by solid dispersion (SD) technique using a novel amphiphilic copolymer, polyvinyl caprolactam–polyvinyl acetate–polyethyleneglycol graft copolymer (Soluplus®). The SD formulations were prepared by the spray drying method with SFN, Soluplus, and sodium lauryl sulfate (SLS) at various weight ratios in water. The optimized SD formulation, which showed the highest dissolution rate in distilled water, was further characterized for surface morphology, crystallinity, dissolution in pH1.2, pH4.0, and pH6.8, and pharmacokinetics in rats. Powder X-ray diffraction and differential scanning calorimetry revealed the amorphous form of SFN in the formulation. In addition, at the oral dosage of 20mg/kg SFN, the SD formulation showed increased Cmax and AUC0–48h by 1.5- and 1.8-fold, compared to those of SFN powder, respectively (p<0.05). These findings suggest that the preparation of SFN-loaded SD using Soluplus could be a promising strategy for improvement of oral bioavailability of SFN.

Development and physicochemical characterization of sirolimus solid dispersions prepared by solvent evaporation method.

The aim of the present investigation was preparation and characterization of sirolimus solid dispersions by solvent evaporation technique to improve its dissolution properties. Polyvinylpyrrolidone (PVP), Poloxamer 188 and Cremophore RH40 were used to prepare the solid dispersions of sirolimus. In vitro dissolution study using USP type I apparatus, were performed in distilled water (containing SLS 0.4%) for pure sirolimus, physical mixtures, Rapamune and prepared solid dispersions. The characterization of solid dispersions was performed using Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC). More than 75% of sirolimus was released within 30 minutes from all prepared solid dispersions. The dissolution rate of all prepared solid dispersion powders were more than physical mixtures. The absence of sirolimus peak in the DSC spectrum of solid dispersions indicated the conversion of crystalline form of sirolimus into amorphous form. The results from FT-IR spectroscopy showed that there was no significant change in the FT-IR spectrum of solid dispersions indicating absence of well-defined interaction between drug and carriers. It was concluded that solid dispersion method, using PVP, Poloxamer 188 and Cremophore RH40 can improve dissolution rate of sirolimus.

Characterization of solid dispersions of Patchouli alcohol with different polymers: effects on the inhibition of reprecipitation and the improvement of dissolution rate

Solid dispersion technique is known to be an effective approach for the polymer to keep drugs stable in the solid state, thereby improving the dissolution rate and oral bioavailability through inhibiting reprecipitation in supersaturated solution. In this study, to evaluate the inhibitory effect of polyethylene glycol-6000 (PEG), Polyvinylpyrrolidone K30 (PVP) and Aminoalkyl methacrylate copolymer (Eudragit), the reprecipitation profiles were observed from supersaturated solutions of Patchouli alcohol (PA) in the presence and absence of the polymers. Furthermore, the dissolution profiles of PA solid dispersions formulated with PEG, PVP or Eudragit were compared for investigating the effect on improving dissolution of each polymer. Solid dispersions formulated with Eudragit were found to result in solution with the highest extent of supersaturation. By contrast, PEG and PVP were less effective. At equivalent supersaturation, all three polymers are capable of mitigating reprecipitation relative to that of PA alone. In addition, in the PA solid dispersion with Eudragit (E-SD (1/3)), the highest concentration of supersaturation of PA was maintained for prolonged time. These results unambiguously indicate that it is imperative to select the appropriate polymer and drug/polymer ratio in addition to considering the stability of the supersaturated solution, which was generated following dissolution of amorphous solid dispersion.

Preparation, characterization and in vitro dissolution of aceclofenac-loaded PVP solid dispersions prepared by spray drying or rotary evaporation method

This study was conducted to enhance dissolution rate of aceclofenac (ACF) with extremely low solubility and high permeability (BCS class II) in water using poly vinyl pyrrolidone (PVP) and sodium lauryl sulfate as carriers. Solid dispersions were prepared by spray drying method and rotary evaporation method using different ratios of ACF and polymers. The characterization of solid dispersions was evaluated by scanning electron microscopy, Fourier transformation infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometer. The dissolution behavior of solid dispersions was compared with pure ACF (API) and Airtal® (Deawoong, Co, Korea) as control groups in simulated phosphate buffer at pH 6.8. The dissolution rate of the drug was affected by nature and amount of polymer used. The prepared solid dispersion of ACF/PVP (1:5) appeared to have the highest dissolution rate. Therefore, solid dispersion techniques of spray drying and rotary evaporation method can be successfully used for the enhancement of the dissolution rate of ACF.

Preparation and Characterization of Solid Dispersions of Rofecoxib

The present study is aimed at improving the dissolution of poorly soluble drug, rofecoxib, using solid dispersion technique. The solid dispersions were prepared in different proportions using hydrophilic carriers like mannitol, and urea. The dissolution rate studies were performed in both simulated gastric fluid and simulated intestinal fluid. It is observed that the dissolution was affected by the acidity of the medium. Solid dispersions gave faster dissolution rate when compared to corresponding physical mixture and pure drug. In vivo absorption and anti-inflammatory activity studies of solid dispersions also confirmed the above results. The DSC thermogram and IR spectra revealed that there is no interaction of Rofecoxib with additives and the drug, rofecoxib is stable in solid dispersions.

Preparation and Characterization of Metformin Hydrochloride − Compritol 888 ATO Solid Dispersion

Metformin hydrochloride (MET) sustained-release solid dispersions (SD) were prepared by the solvent evaporation and closed melt method, using compritol 888 ATO as the polymer with five different drug-carrier ratios. Characterization of solid dispersion was carried out by Fourier Transform Infrared (FTIR) spectroscopy, ultraviolet (UV) spectroscopy, Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD). The FTIR and UV studies suggested that no bond formation had occurred between the polymer and the drug. DSC and XPRD results ruled out any interaction or complex formation between the drug and the polymer. The formulated SD had acceptable physicochemical characters and SD with a 1 : 4 drug : Polymer ratio, which released the drug over an extended period of eight-to-ten hours. The data obtained from the in vitro release studies were fitted with various kinetic models and were found to follow the Korsmeyer-Peppas equation. The prepared SD showed good stability over the studied time period. The solvent evaporation method was found to be more helpful than the closed melt method, giving the sustained release action. The SD with a 1 : 4 ratio of drug to polymer, by the solvent evaporation method, was selected as the most effective candidate for the subsequent development of a well-timed, sustained-release dosage form of the drug.

Preparation and Physicochemical Characterization of Solid Dispersion of Aceclofenac Formulated by Solvent Evaporation Method

Preparation and Physicochemical Characterization of Solid Dispersion of Aceclofenac Formulated by Solvent Evaporation Method