Drug Dissolution Rate Research Articles

Preparation of Aspirin Nanosuspension by Antisolvent Precipitation Method

Preparation of Aspirin Nanosuspension by Antisolvent Precipitation Method

Boosting the mechanical strength and solubility-enhancement properties of hydroxypropyl-β-cyclodextrin nanofibrous films

2-hydroxypropyl-β-cyclodextrin (HPβCD) nanofiber films have high surface-to-volume ratio and show high dissolution rate of hydrophobic drugs. However, the solubility-enhancement effect of HPβCD films may not be enough to include an effective dose in a sublingually administrable film. Moreover, unmodified HPβCD films are very brittle and difficultly transported and/or handled. So, the addition of polyethylene glycol (PEG) as a plasticizer was suggested to improve their ultimate tensile strength (UTS) and solubilization of hydrophobic drugs. Accordingly, six nanofiber films were developed and characterized, using three molecular weights of PEG (400, 1500 and 6000 Da) with two concentrations each (1:100 and 2:100 PEG:HPβCD), in addition to the unmodified HPβCD nanofibrous film. The results revealed that adding 1:100 of PEG 400 increases the UTS (∼2-fold) and the average fiber diameter (AFD) (∼3-fold). Moreover, the addition of PEG 400 significantly increased the solubility of two hydrophobic model drugs; coumarin (up to 7.7-fold of the original solubility) and 2-nitroimidazole (up to 1.6-fold of the original solubility). However, with higher PEG concentration/molecular weight, both AFD and UTS of the films decreased. On the other hand, it was noted that the solubility of the two model drugs decreased upon using 1500-Da PEG, and then increased with 6000-Da PEG.

Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement.

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO2) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus® (SOL) at temperatures below polymer’s glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug–polymer ratio on the successful preparation of SDs. The SIM–SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO2 processing conditions and drug–polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM–SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM–SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.

Preparation of Solid Dispersion and Its Application in Functional Food

Solid dispersion is considered to be one of the most successful ways to solve the poor water-solubility and dissolution rate of raw materials and drugs in the pharmaceutical field. Due to its unique advantages in solving the problems of water-solubility, poor stability and low bioavailability of functional active ingredients, solid dispersion has been gradually applied to the research and development of functional food. This paper reviews and summarizes the research status and development trend of solid dispersion from four aspects: classification, preparation technology, stability and its application in functional food. Combined with the background of the current post epidemic era, new requirements are put forward for the further application of solid dispersion in the food field in the future, and it is also hoped to provide new reference and research ideas for the further application of solid dispersion in the food field.

Effect of Counterions on Dissolution of Amorphous Solid Dispersions Studied by Surface Area Normalized Dissolution.

Solubility enhancement has become a common requirement for formulation development to deliver poorly water soluble drugs. Amorphous solid dispersions (ASDs) and salt formation have been two successful strategies, yet there are opportunities for further development. For ASDs, drug-polymer phase separation may occur at high drug loadings during dissolution, limiting the increase of drug loadings in ASD formulations. For salt formation, a salt form with high crystallinity and sufficient solid-state stability is required for solid dosage form development. This work studied the effect of counterions on the dissolution performance of ASDs. Surface area normalized dissolution or intrinsic dissolution methodology was employed to eliminate the effect of particle size and provide a quantitative comparison of the counterion effect on the intrinsic dissolution rate. Using indomethacin (IMC)-poly(vinylpyrrolidone-co-vinyl acetate) ASD as a model system, the effect of different bases incorporated into the ASD during preparation, the molar ratios between the base and IMC, and the drug loadings in the ASD were systematically studied. Strong bases capable of ionizing IMC significantly enhanced drug dissolution, while a weak base did not. A physical mixture of a strong base and the ASD also enhanced the dissolution rate, but the effect was less pronounced. At different base to IMC molar ratios, dissolution enhancement increased with the base to IMC ratio. At different drug loadings, without a base, the IMC dissolution rate decreased with the increase of drug loading. After incorporating a strong base, it increased with the increase of drug loading. The observations from this study were thought to be related to both the ionization of IMC in ASDs and the increase of microenvironment pH by the incorporated bases. With the significant enhancement of the drug dissolution rate, our work provides a promising approach of overcoming the dissolution limitation of ASD formulations at high drug loadings.

Carboxylic acid decorated silica aerogel nanostructure as drug delivery carrier

Surface functionalization of silica aerogel could pioneer great utilities, including the modified release of loaded drugs through the specific interaction that emerged. In this work, the effect of carboxylic modification of silica aerogel on drug loading capacity and drug dissolution rate was studied to evaluate as celecoxib (CCB) delivery carrier. The modification was successfully carried out on calcined ambient pressure dried silica aerogel (SA-OH) through two-step treating with N-(2-Aminoethyl)-3-aminopropyltrimethoxysilane (AEAPTES) and then succinic anhydride. The characterization methods of FT-IR, FE-SEM, nitrogen adsorption-desorption analysis, TGA, DSC, XRD, zeta-potential measurements, and UV-spectrophotometry were used to study the surface modification and drug loading process systematically. The results have shown that the modification to grafting the terminal –COOH groups on the SA-OH were successfully carried out. The modified aerogels have a similar mesoporous structure to the original ones with a smaller mean pore size. After CCB loading on the carriers, its crystallinity state converts to the non-crystalline and amorphous in the SA-OH and SA-COOH carriers, respectively. Besides, loading on SA-COOH benefits the COO − - NH 3 + bonding between carrier and drug functional groups. Drug release results displayed a faster drug dissolution from both carriers than the pure drug, and the controlled release rate was observed from SA-COOH/CCB compared with the SA-OH/CCB due to the existence of stronger bonding and smaller pore size. It was found that SA-COOH has good potential, considering the ability to adjust drug dissolution and exhibiting good biocompatibility on exposure to model cell line. • The silica aerogel with carboxylic acid functional groups (SA-COOH) was successfully synthesized. • The drug release was modified due to molecular drug state and drug-carrier interaction. • Cell viability assay was confirmed the biocompatibility of SA-COOH.

Statistical Designing and Characterization of Valsartan Oral Disintegrating Tablet

The present study involves the formulation and characterization of valsartan (VT) oral disintegrating tablets by using crospovidone (CP) and Hibiscus rosasinensis (HRS) mucilage as complexing agent. Valsartan (VT), anti-hypertensive drug (class II) is an orally active non-peptide triazole-derived antagonist of angiotensin II. The direct compression method was used to obtain 13 such formulations, and the tablets obtained were evaluated for drug content, hardness, friability (FT), disintegration time (DT) and dissolution rate. A significant increase in the dissolution rate of VT was obtained. FTIR and DSC studies showed no interaction between the drug and excipients. The amount of CP (X₁) and amount to HRS mucilage (X₂) is selected for 3² factorial designs. The DT (Y₁), FT (Y₂) and % drug released at 25 min (Y₃) interval were taken as the response variables. X₁ and X₂ represents the result of changing the variable at a time from low level to high level. The interaction terms (X₁X₂, X₁², X₂², X₁²X₂ and X₁X₂²) exhibited that Y₁, Y₂ and Y₃ had changed simultaneously (as analyzed by Design expert software 8 version). The contour and 3D plots revealed that there is an effect of X₁ and X₂ with the interaction on Y₁, Y₂ and Y₃. F₂ formulation exhibited minimum errors with CP and HRS in response to dependable variables which is concluded as best formulation.

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.

Karakterisasi Sistem Dispersi Padat Meloksikam Dengan Matriks PEG 6000 Dan Poloxamer 188 Dibuat Dengan Menggunakan Metode Peleburan

Meloxicam is included in the class II Biopharmaceutical Classification System (BCS). This drug has low solubility and high permeability. The solubility is one of the factors that affect in the dissolution rate of drug. One of the effort to increase dissolution of meloxicam is by forming a solid dispersion system made using melting method. The addition of PEG 6000 and poloxamer 188 carriers determine in the solid dispersion system aims to increase the dissolution rate of meloxicam. The purpose of this study is to characterize the meloxicam solid dispersion system with PEG 6000 and poloxamer 188 matrices at a ratio of 99:1 and 98:2 made by the melting method when compared with the physical mixture and its pure compound using Powder X-Ray Diffaction, DSC and FTIR. The results of meloxicam solid dispersion with a ratio 99:1 and 98:2 showed the disappearance of the typical peak of meloxicam at an angel of 2θ 6.5° and 11.2°. The thermogram data using DSC shows a decrease in melting point of solid dispersion system with a ratio of 99:1 and 98:2 namely 64.33°C and 64.21°C. The result of the characterization of meloxicam solid dispersion with FTIR showed that the identified spectrum were in the spectrum range of meloxicam, PEG 6000, poloxamer 188 indicating there was no incteraction in the meloxicam solid dispersion system. Keywords: Meloxicam, PEG 6000, Poloxamer 188, Solid Dispersion, Melting Method, Characterization

Erlotinib complexation with randomly methylated β-cyclodextrin improves drug solubility, intestinal permeability, and therapeutic efficacy in non-small cell lung cancer

The purpose of this study was to investigate the impact of anticancer drug erlotinib-randomly methylated-β-cyclodextrin complex (ERL-RAMEB CD) on drug solubility and dissolution rate. Phase solubility study showed erlotinib displayed maximum solubility in RAMEB CD solution and the stability constant (Kc) was calculated to be 370 ± 16 M−1. The optimal formulation was obtained with ERL-RAMEB CD in a 1:1 molar ratio using the co-lyophilization technique. Differential scanning calorimetry (DSC) and Scanning electron microscopy (SEM) verified the inclusion of complex formation. In vitro dissolution study confirmed ERL-RAMEB CD as a favorable approach to increase drug dissolution with a 1.5-fold increase than free ERL at 1 h. An improved dissolution with ∼88.4% drug release at 1 h was observed, in comparison with Erlotinib with ∼58.7% release in 45 min. The in vitro cytotoxicity results indicated that the ERL-RAMEB CD inclusion complex reduced cell viability than free erlotinib. Caco-2 cell uptake that is indicative of drug intestinal permeability resulted in a 5-fold higher uptake of ERL-RAMEB CD inclusion complex than the ERL solution. Hence, ERL-RAMEB CD complexation displays a strong potential to increase dissolution and permeability of erlotinib leading eventually to enhanced oral bioavailability.

Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance.

The interaction between meloxicam and sulfonatocalix[4]naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix[4]naphthalene. The solubility phase diagram was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix[4]naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release (p ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR10 in the investigated media, with average values ranging from 5.4–65.28 folds and 7.3–90.7, respectively. In conclusion, sulfonatocalix[4]naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.

Combination of Phospholipid Complex and Matrix Dispersion.

Phospholipid complexation, despite being a successful, versatile, and burgeoning strategy, stickiness of phospholipids leads to suboptimal dissolution rate of drugs. This work was undertaken to fabricate simvastatin-phospholipid complex (SIM-PLC)-loaded matrix dispersion (SIM-PLC-MD) using Soluplus® as carrier material, to augment dispersibility and dissolution of SIM-PLC without altering complexation between simvastatin (SIM) and phospholipid. SIM-PLC and SIM-PLC-MD were prepared using solvent evaporation and discontinuous solvent evaporation techniques, respectively. The successful complexation was substantiated by FTIR method. Besides, PXRD and SEM studies disclosed the absence of crystallinity of SIM in both SIM-PLC and SIM-PLC-MD. The TEM analysis monitored the self-assembly of SIM-PLC and SIM-PLC-MD into colloidal structures, which could be correlated with redispersion in GIT fluids upon oral administration. The considerable increase in hydrophilicity of SIM-PLC-MD and SIM-PLC as evident from partition coefficient experiment can further be correlated with their remarkably improved solubility profiles in the following pattern: SIM-PLC-MD˃SIM-PLC˃SIM. Correspondingly, improved dispersibility of SIM-PLC-MD in comparison to SIM-PLC can be accountable for accelerated dissolution rate by 2.53-fold and 1.5-fold in pH 1.2 and 6.8 conditions, respectively. The oral pharmacokinetic evaluation in Sprague Dawley (SD) rats revealed 3.19-fold enhancement in oral bioavailability of SIM through SIM-PLC-MD when compared with plain SIM, whereas 1.83-fold increment was observed in the case of SIM-PLC. Finally, the efficacy experimentation in SD rats revealed that SIM-PLC-MD significantly reduced triglycerides and cholesterol levels in comparison to SIM and SIM-PLC. These outcomes suggest that a matrix dispersion strategy improves oral bioavailability and hypolipidemic activity of SIM.

Enhance dissolution rate and solubility of solid drugs through pharmaceutical deep eutectic solvents

Pharmaceutical active ingredients are usually sold in the markets in the form of solid drugs. These drugs are often associated with some problems like polymorphism, bioavailability and low solubility.  In this study, deep eutectic solvents (DESs) are used to change solid drugs into liquids, which may provide a potential solution to these problems. This research describes synthesis and design of pharmaceutical deep eutectic solvents (PDESs) from hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs), which are one of the key parts of medicine improvement. Differential scanning calorimetry (DSC) was used to measure glass transition temperatures for the prepared PDESs and fourier transform infrared spectroscopy (FT-IR) was utilized to clarify hydrogen bond formation between HBDs and HBAs. Also, dissolution test apparatus and UV-Vis spectroscopy were used to measure dissolution rate and concentration of the prepared PDESs in this work.

Formulation and In-Vitro Evaluation of Meloxicam Solid Dispersion using Natural Polymers.

Meloxicam (MLX) is non-steroidal anti -inflammatory, poorly water soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Solid dispersion (SD) is an effective technique for enhancing the solubility and dissolution rate of such drug.
 The present study aims to enhance the solubility and the dissolution rate of MLX by SD technique by solvent evaporation method using sodium alginate (SA), hyaluronic acid (HA), collagen and xyloglucan (XG) as gastro-protective hydrophilic natural polymers.
 Twelve formulas were prepared in different drug: polymer ratios and evaluated for their, percentage yield, drug content, water solubility, dissolution, crystal lattice using powder X-ray diffraction (PXRD) and studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-polymer interaction.
 All the prepared showed improvement of drug solubility except that prepared with HA. The best result was obtained with formula SD1 (MLX: SA 1:1) that showed a high percentage yield (97), high drug content (97.4±0.05) and increase in solubility compared to solubility of pure MLX with improved dissolution rate. the PXRD study revealed the conversion of the drug to amorphous form without chemical interaction according to FTIR results

Studying the Impact of the Temperature and Sorbed Water during Microwave-Induced In Situ Amorphization: A Case Study of Celecoxib and Polyvinylpyrrolidone.

Microwave-induced in situ amorphization of a drug into a polymeric amorphous solid dispersion (ASD) has been suggested to follow a dissolution process of the drug into the polymeric network, at temperatures above the glass transition temperature (Tg) of the polymer. Thus, increasing the compact temperature, above the Tg of the polymer, is expected to increase the rate of drug dissolution in the mobile polymer, i.e., the rate of amorphization, in a direct proportional fashion. To test this hypothesis, the present study aimed at establishing a linear correlation between the compact temperature and the rate of drug amorphization using celecoxib (CCX) and the polymers polyvinylpyrrolidone (PVP) 12 and PVP17 as the model systems. Water sorbed into the drug–polymer compacts during 2 weeks of storage at 75% relative humidity was used as the dielectric heating source for the present drug amorphization process, and therefore directly affected the compact temperature during exposure to microwave radiation; the loss of water during heating was also studied. For this, compacts prepared with 30 wt% CCX, 69.5 wt% PVP12 or PVP17 and 0.5 wt% magnesium stearate (lubricant) were conditioned to have a final water content of approx. 20 wt%. The conditioned compacts were exposed to microwave radiation for 10 min at variable power outputs to achieve different compact temperatures. For compacts containing CCX in both PVP12 and PVP17, a linear correlation was established between the measured compact end temperature and the rate of drug amorphization during 10 min of exposure to microwave radiation. For compacts containing CCX in PVP12, a fully amorphous ASD was obtained after 10 min of exposure to microwave radiation with a measured compact end temperature of 71 °C. For compacts containing CCX in PVP17, it was not possible to obtain a fully amorphous ASD. The reason for this is most likely that a fast evaporation of the sorbed water increased the Tg of the conditioned drug–polymer compacts to temperatures above the highest reachable compact temperature during exposure to microwave radiation in the utilized experimental setup. Supporting this conclusion, evaporation of the sorbed water was observed to be faster for compacts containing PVP17 compared to compacts containing PVP12.

Nanocrystals for Improving Oral Bioavailability of Drugs: Intestinal Transport Mechanisms and Influencing Factors.

With the limitation of solubility and dissolution rate of insoluble drugs, following oral administration, they would rifely prove poor and volatile bioavailability, which may fail to realize its therapeutic value. The drug nanocrystals are perceived as effective tactic for oral administration of insoluble drugs attributes to possess many prominent properties such as elevating dissolution rate and saturation solubility, high drug loading capacity, and improving oral bioavailability. Based on these advantages, the application of nanocrystals in oral drug delivery has acquired significant achievement, and so far more than 20 products of drug nanocrystals have been confirmed in the market. However, the oral absorption of drug nanocrystals is still facing huge challenges due to the limitation of many factors. Intrinsic properties of the drugs and complex physiological environment of the intestinal tract are the two most important factors affecting the oral bioavailability of drugs. In addition, the research on the multi-aspect mechanisms of nanocrystals promoting gastrointestinal absorption and bioavailability has been gradually deepened. In this review, we summarized recent advances of the nanocrystals delivered orally, and provided an overview to the research progress for crossing the intestinal tract transport mechanisms of the nanocrystals by some new research techniques. Meanwhile, the factors relevant to the transport of drug nanocrystals were also elaborated in detail. Graphical Abstract.

Determination of Intrinsic Drug Dissolution and Solute Effective Transport Rate during Laminar Fluid Flow at Different Velocities.

The objective of this study was to determine the intrinsic drug dissolution rate (IDR) and the solute effective transport rate of some drugs, using a single particle dissolution technique, satisfying qualified dissolution conditions. The IDR of three poorly water-soluble compounds was measured in milli-Q water using four different fluid velocities. The enveloped surface area of the particles was calculated from the projected area and the perimeter of the particle observed in the microscope. Furthermore, computational fluid dynamics (CFD) simulations were used to theoretically investigate the flow conditions and dissolution rate, comparing box shaped particles and spherical particles with similar dimensions and surface area as the particles used the experiments. In this study, the IDR measurement of the single particles was determined within 5–60 min using particles with an initial projected area diameter () between 37.5–104.6 µm. The micropipette-assisted microscopy technique showed a good reproducibility between individual measurements, and the CFD simulations indicated a laminar flow around the particles at all flow velocities, even though there were evident differences in local particle dissolution rates. In conclusion, the IDR and solute effective transport rate were determined under well-defined fluid flow conditions. This type of approach can be used as a complementary approach to traditional dissolution studies to gain in-depth insights into the dissolution process of drug particles.

A Review on Formulation and Development of Solid Self-Nano Emulsifying Drug Delivery Systems

This article describes current strategies to enhance aqueous solubility and dissolution rate of poor soluble drugs. Most drugs in the market are lipophilic with low or poor water solubility. There are various methods to enhance solubility: co-solvency, particle size reduction, salt formation and Self Nanoemulsifying drug delivery systems, SEDDS is a novel approach to enhance solubility, dissolution rate and bioavailability of drugs. The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Oral route is the most convenient route for non-invasive administration. S-SNEDDS has more advantages when compared to the liquid self-emulsifying drug delivery system. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants were selected to formulate Liquid SNEDDS these formulated liquid self-nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques; they are spray drying; freeze drying and fluid bed coating technique; extrusion, melting granulation technique. Liquid SNEDDS has a high ability to improve dissolution and solubility of drugs but it also has disadvantages like incompatibility, decreased drug loading, shorter shelf life, ease of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis.

The anti-inflammatory effects of cannabidiol and cannabigerol alone, and in combination

Introduction/background and purposeStudies with Cannabis Sativa plant extracts and endogenous agonists of cannabinoid receptors have demonstrated anti-inflammatory, bronchodilator, and antitussive properties in the airways of allergic and non-allergic animals. However, the potential therapeutic use of cannabis and cannabinoids for the treatment of respiratory diseases has not been widely investigated, in part because of local irritation of airways by needing to smoke the cannabis, poor bioavailability when administered orally due to the lipophilic nature of cannabinoids, and the psychoactive effects of Δ9-Tetrahydrocannabinol (Δ9-THC) found in cannabis. The primary purpose of this study was to investigate the anti-inflammatory effects of two of the non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) alone and in combination, in a model of pulmonary inflammation induced by bacterial lipopolysaccharide (LPS). The second purpose was to explore the effects of two different cannabinoid formulations administered orally (PO) and intraperitoneally (IP). Medium-chain triglyceride (MCT) oil was used as the sole solvent for one formulation, whereas the second formulation consisted of a Cremophor® EL (polyoxyl 35 castor oil, CrEL)-based micellar solution. ResultsExposure of guinea pigs to LPS induced a 97 ± 7% and 98 ± 3% increase in neutrophils found in bronchoalveolar lavage fluid (BAL) at 4 h and 24 h, respectively. Administration of CBD and CBG formulated with MCT oil did not show any significant effects on the LPS-induced neutrophilia measured in the BAL fluid when compared with the vehicle-treated groups. Conversely, the administration of either cannabinoid formulated with CrEL induced a significant attenuation of the LPS induced recruitment of neutrophils into the lung following both intraperitoneal (IP) and oral (PO) administration routes, with a 55–65% and 50–55% decrease in neutrophil cell recruitment with the highest doses of CBD and CBG respectively. A combination of CBD and CBG (CBD:CBG = 1:1) formulated in CrEL and administered orally was also tested to determine possible interactions between the cannabinoids. However, a mixture of CBD and CBG did not show a significant change in LPS-induced neutrophilia. Surfactants, such as CrEL, improves the dissolution of lipophilic drugs in an aqueous medium by forming micelles and entrapping the drug molecules within them, consequently increasing the drug dissolution rate. Additionally, surfactants increase permeability and absorption by disrupting the structural organisation of the cellular lipid bilayer. ConclusionIn conclusion, this study has provided evidence that CBD and CBG formulated appropriately exhibit anti-inflammatory activity. Our observations suggest that these non-psychoactive cannabinoids may have beneficial effects in treating diseases characterised by airway inflammation.

Development of rebamipide-loaded spray-dried microsphere using distilled water and meglumine: physicochemical characterization and pharmacokinetics in rats

In this study, a novel rebamipide-loaded spray-dried microsphere (RSM) with enhanced drug solubility and oral bioavailability has been developed utilizing meglumine, an alkalizing agent. The influence of carriers on the drug solubility alone, and the solubility and dissolution of the drug in the RSM was investigated. Among the alkalizing agents and hydrophilic polymers tested, meglumine and polyvinyl alcohol (PVA) showed the highest drug solubility and dissolution rate, respectively. Many RSMs were manufactured with various amounts of meglumine and PVA using distilled water, and their drug solubility and dissolution were determined. The physicochemical properties, dissolution and pharmacokinetics of the chosen RSM in rats were assessed compared to the rebamipide powder and commercial tablet. Among the RSMs tested, the one composed of rebamipide, meglumine and PVA at a weight ratio of 3:1.75:6 showed the highest drug solubility and dissolution. This RSM with a smooth spherical form significantly decreased the particle size and modified the amorphous rebamipide. Furthermore, the drug solubility, dissolution, plasma concentrations, AUC and Cmax values of RSM were significantly higher than those of drug powder and commercial tablet. Thus, this RSN system developed with distilled water and meglumine is recommended as an oral water-soluble rebamipide-loaded pharmaceutical product.