Preparation and Evaluation of Silymarin-Loaded Solid Eutectic for Enhanced Anti-Inflammatory, Hepatoprotective Effect: In Vitro–In Vivo Prospect

Solubility of phytochemicals is a major concern for drug delivery, permeability, and their biological response. However, advancements in the novel formulation technologies have been helping to overcome these challenges. The applications of these newer technologies are easy for commercialization and high therapeutic outcomes compared to conventional formulations. Considering these facts, the present study is aimed to prepare a silymarin-loaded eutectic mixture with three different ratios of Polyvinylpyrrolidone K30 (PVP K30) and evaluating their anti-inflammatory, and hepatoprotective effects. The preliminary phytochemical and characterization of silymarin, physical mixture, and solid dispersions suggested and successfully confirmed the formation of solid dispersion of silymarin with PVP K30. It was found that the solubility of silymarin was increased by 5-fold compared to pure silymarin. Moreover, the in vitro dissolution displayed that 83% of silymarin released within 2 h with 2.8-fold increase in dissolution rate compared to pure silymarin. Also, the in vivo study suggested that the formulation significantly reduced the carbon tetrachloride- ( 0.8620 ± 0.05034 ∗ ∗ for 1 : 3 ratio), paracetamol- ( 0.7300 ± 0.01517 ∗ ∗ for 1 : 3 ratio), and ethanol- ( 0.8100 ± 0.04037 ∗ ∗ for 1 : 3 ratio) induced hepatotoxicity in rats. Silymarin solid dispersion was prepared using homogenization methods that have prominent anti-inflammatory effect ( 0.6520 ± 0.008602 ∗ ∗ with 8.33%) in carrageenan-induced rat paw model.

Preparation and Evaluation of a Powdered Rebamipide Mouthwash as In-Hospital Formulation: Considering Dispersion before Use in Patients

In Japan, rebamipide (RB) mouthwash (RB-MW) for oral mucositis induced by cancer chemotherapy has been prepared using in-hospital formulation. Usually, RB-MW is prepared by dispersing crushed commercial RB tablets in the dispersion medium; however, uniformity is difficult to obtain due to low solubility. The current study aims is to prepare homogenously dispersed formulations using the fine particles of crushed tablets by a method that is convenient for hospital use. Commercial RB tablets were pre-milled at different milling times as “RB-Ts”. A ground mixture was then prepared by co-grinding the RB-Ts with HPC-L or PVP K30 via a benchtop ball milling machine (MM400). The physicochemical properties of samples were evaluated for PXRD, FTIR, turbidity, particle size, and solubility. Although the milling of RB tablets decreased the crystallinity, the length of milling time did not affect them. In contrast, grinding using MM400 significantly decreased RB crystallinity; their PXRD patterns showed a halo, suggesting the amorphization of RB crystals by grinding. Although solubility and turbidity seemed to be affected by the type of polymer rather than the particle size, every ground mixture showed high dispersibility. Thus, grinding the RB-Ts with polymers appeared to be the most promising way to obtain stable dispersion as an in-hospital formulation.

Effect of Surfactants and Polymers on the Dissolution Behavior of Supersaturable Tecovirimat-4-Hydroxybenzoic Acid Cocrystals

(1) Background: Pharmaceutical cocrystals have attracted remarkable interest and have been successfully used to enhance the absorption of poorly water-soluble drugs. However, supersaturable cocrystals are sometimes thermodynamically unstable, and the solubility advantages present a risk of precipitation because of the solution-mediated phase transformation (SMPT). Additives such as surfactants and polymers could sustain the supersaturation state successfully, but the effect needs insightful understanding. The aim of the present study was to investigate the roles of surfactants and polymers in the dissolution-supersaturation-precipitation (DSP) behavior of cocrystals. (2) Methods: Five surfactants (SDS, Poloxamer 188, Poloxamer 407, Cremophor RH 40, polysorbate 80) and five polymers (PVP K30, PVPVA 64, HPC, HPMC E5, CMC-Na) were selected as additives. Tecovirimat-4-hydroxybenzoic (TEC-HBA) cocrystals were chosen as a model cocrystal. The TEC-HBA cocrystals were first designed and verified by PXRD, DSC, SEM, and FTIR. The effects of surfactants and polymers on the solubility and dissolution of TEC-HBA cocrystals under sink and nonsink conditions were then investigated. (3) Results: Both the surfactants and polymers showed significant dissolution enhancement effects, and most of the polymers were more effective than the surfactants, according to the longer Tmax and higher Cmax. These results demonstrate that the dissolution behavior of cocrystals might be achieved by the maintained supersaturation effect of the additives. Interestingly, we found a linear relationship between the solubility and Cmax of the dissolution curve for surfactants, while no similar phenomena were found in solutions with polymer. (4) Conclusions: The present study provides a basis for additive selection and a framework for understanding the behavior of supersaturable cocrystals in solution.

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Different from previously reported co-amorphous systems, a co-amorphous curcumin-magnolol (CUR-MAG CM) system, as compared with its crystalline counterparts, exhibited decreased dissolution due to its aggregation during dissolution. The main purpose of the present study is to deaggregate CUR-MAG CM to optimize drug dissolution and explore the deaggregation mechanism involved. Herein, a small amount of polymer (HPMC, HPC, and PVP K30) was co-formulated at 5% (w/w) with CUR-MAG CM as ternary co-amorphous systems. The polymer addition changed the surface properties of CUR-MAG CM including improved water wettability enhanced surface free energy, and hence exerted a deaggregating effect. As a result, the ternary co-amorphous systems showed faster and higher dissolution as compared with crystalline CUR/MAG and CUR-MAG CM. In addition, the nucleation and crystal growth of dissolved CUR and MAG molecules were significantly inhibited by the added polymer, maintaining a supersaturated concentration for a long time. Furthermore, polymer addition increased the Tg of CUR-MAG CM, potentially involving molecular interactions and inhibiting molecular mobility, resulting in enhanced physical stability under 25 °C/60% RH and 40 °C/75% RH conditions. Therefore, this study provides a promising strategy to optimize the dissolution and physical stability of co-amorphous systems by deaggregation and crystallization inhibition via adding small amounts of polymers.

Preparation of Carbopol 934 Based Ketorolac Tromethamine Buccal Mucoadhesive Film: In Vitro, Ex Vivo, and In Vivo Assessments

The goal of present investigation was to formulate and evaluate ketorolac tromethamine (KTM) mucoadhesive buccal films. The films were prepared by solvent evaporation method using PVP K30, HPMC K4M, HPMC K15M, carbopol 934, chitosan, and sodium alginate as polymers and propylene glycol as plasticizer. The films were evaluated for thickness, weight variation, folding endurance, surface pH, swelling index, in vitro residence time, in vitro diffusion, release kinetics, ex vivo permeation, in vitro-ex vivo correlation, and in vivo pharmacological activities such as anti-inflammatory and analgesic activity. Thickness, weight, drug content, and folding endurance were found to be uniform for the films. Surface pH was 6.85 ± 0.10 , and swelling index was the highest ( 27.27 ± 0.37 ) for the best film containing carbopol 934 along with sodium alginate and PVP K 30 (formulation code F2). In vitro residence time was greater than 5 h, and in vitro % drug release was 98.71% for F2. It exhibited 55.49% of swelling inhibition at 5 h, and above 38.88% was maintained at even 8 h. The film F2 has shown maximum analgesic response of 17 sec at 5 h, and the response of 11 sec was maintained at even 8 h. The anti-inflammatory and analgesic effect of F2 was found be maximum while sustaining the effect for prolonged period when compared to free drug solution. Thus, KTM mucoadhesive buccal film containing carbopol 934, sodium alginate, and PVP K30 could be an effective alternative for conventional therapy with improved efficacy.

Rheological Properties and Its Effect on the Lubrication Mechanism of PVP K30 and PVP 40-50 G as Artificial Synovial Fluids

The effect of polyvinylpyrrolidone (PVP) on the rheological properties of joint prostheses is still unclear, despite its good lubricity and biocompatibility. In the present work, PVP K30 and PVP 40-50 G solutions at different concentrations were analyzed for rheological and lubrication properties. The rheological properties of the samples were measured at a shear rate range of 0–1800 s−1 (advanced air bearing rheometer Bohlin Gemini 2 and Plate MCR 72/92 rheometer for PVP30 and PVP 40-50 G, respectively). It was found that both the viscosity and shear stress of the samples reduced with a shear rate increase. PVP 40-50 G/sterile water showed higher viscosity as compared to the PVP K30/sterile water sample at a lower shear rate. However, at a higher shear rate, the PVP K30 sample produced better results. Further numerical study results showed the pressure and molecular viscosity distributions. The inclusion of PVP improved the load caring capacity and hence, it is a promising lubrication additive for artificial joints.

Pengaruh Kombinasi Polimer Polivinil Pirolidon dan Etil Selulosa terhadap Karakteristik dan Uji Penetrasi Formulasi Transdermal Patch Ekstrak Bawang Dayak (Eleutherine palmifolia (L)

The transdermal patch can deliver the active substance with good bioavailability, then made formulations of such preparations from dayak onion extract, which has a compound content of flavonoids, with a combination of polymer PVP K30 and ethyl cellulose to produce transdermal patches with good physical evaluation and penetration. The research aims to carry out the effect and ideal formulation of transdermal patches of dayak onion extract with a combination of polymers PVP K30 and ethyl cellulose based on physical evaluation and penetration—manufacture of transdermal patches using the solvent evaporation method. Physical evaluation includes organoleptic testing, weight uniformity, thickness, folding resistance, and moisture testing. Then evaluate the penetration of the active substance using Franz diffusion cells. Analyze data with One Way ANOVA. The physical evaluation results of weight uniformity, patch thickness, folding resistance, and moisture test of transdermal patches on F1, F2, F3, and F4 meet the requirements. As for the results of penetration tests, F1, F2, F3, and F4 can be penetrated from 120 minutes to 180 minutes with the concentration of active substances that are linearly penetrated. The combination of polymers PVP K30 and ethylcellulose has affected the physical evaluation of transdermal patches of dayak onion extract. Based on the physical evaluation and penetration test in vitro obtained, the most optimal formula results are F3 with comparison PVP K30 and ethyl cellulose (100:300).

Physicochemical Characterization and Dissolution Enhancement of Bilastine by Solid Dispersion

The solid dispersions of Bilastine with HPMC, PVP K30 and HPC have been prepared in different weight ratios by using solvent evaporation method. DSC was used to characterize the samples of solid dispersions and pure drug. Drug found compatible with the excipients. The highest improvements in solubility and in-vitro drug release were observed in solid dispersion prepared with HPC (F14) by solvent evaporation method. The increased dissolution rate of drug from solid dispersion may be due to surface tension lowering effect of polymer to the medium and increased wettability and dispersibility of drug. Hence, F14 Solid dispersion with the HPC carrier considered as most satisfactory among all solid dispersions.

FORMULATION OF SOLID DISPERSIONS FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF SIMVASTATIN

Objective: The objective of the present work was to formulate the solid dispersions of simvastatin for enhancement of its aqueous solubility and dissolution rate. Methods: In the present study, solid dispersions of simvastatin were prepared by Kneading and Solvent evaporation methods. The polymeric carriers like Polyethylene glycol (PEG) 6000 and Polyvinyl Pyrrolidone (PVP) K30 were used in different ratios (ratio of drug: carrier was 1:1, 1:2) to formulate solid dispersions. The prepared solid dispersions were characterized by differential scanning calorimetry (DSC), Fourier transforms infrared spectroscopy (FTIR), and evaluated for drug content, percentage yield, saturation solubility, in vitro dissolution studies. The best formula of the solid dispersion was selected according to the solubility and dissolution data. Results: The F7 formulation was found to be an optimized formulation containing PVP K30 in the ratio 1:1 prepared by solvent evaporation technique. The Drug content was found to be higher i.e. 94.89 in the F7 batch. The FT-IR spectra revealed that there was no interaction between drugs and carriers. DSC thermogram indicated entrapment of simvastatin in PVP K30 and the conversion of crystalline simvastatin into an amorphous form. The F7 formulation showed maximum drug release i.e. 98.60% in 60 min which is 2 times greater than pure drug making it an optimized formulation. Conclusion: The solubility of simvastatin was successfully enhanced through the solid dispersion technique. Solid dispersions prepared with solvent evaporation method were more soluble than solid dispersions prepared with kneading method with carrier PVP K30.

SOLID DISPERSION FOR INCREASING DISSOLUTION RATE OF SODIUM DICLOFENAC WITH VARIATIONS OF POLYVINYL PYRROLIDONE K30

Diclofenac sodium is included in class II category based on biopharmaceutics classification system (BCS), sodium diclofenac has low solubility and high permeability. Low solubility will affect absorption of drugs in body because rate of dissolution will decrease. PVP K30 is inert carrier that dissolves easily in water and can affect solubility of an active drug substance. To know solid dispersion system increasing dissolution rate of sodium diclofenac by adding variations concentration of PVP K30. Solid dispersion uses solvent method with variations concentration of PVP K30 1:3, 1:5, 1:7 and 1:9. Test physical properties of solid dispersions using a moisture test and compressibility. Solid dispersion dissolution test using type 2 dissolutions test and determination of concentration using UV-VIS spectrophotometry. Test results were analyzed using One Way ANOVA and continued test. Solid dispersion has a good physical whit moisture percentage not >5% and compressibility not >20%. Solid dispersion of sodium diclofenac with addition of PVP K30 can increase dissolution rate compared to pure sodium diclofenac (p<0,05) with highest at ratio 1:7. Each comparison has significant difference (p<0,05) expect in ratio 1:9. Solid dispersion of sodium diclofenac with PVP K30 can increase dissolution rate of pure sodium diclofenac.