Liquisolid Technology Research Articles

Design and development of Fujicalin-based axitinib liquisolid compacts for improved dissolution and bioavailability to treat renal cell carcinoma

Poor dissolution of axitinib (AXT) limits its effectiveness through the oral route. The present study investigated, prospective of liquisolid (LS) technology to improve dissolution rate and oral bioavailability of AXT to treat renal cell carcinoma. LS compacts were fabricated with PEG 200, Fujicalin SG, and Aerosil 200 as solvent, carrier, and coat material, respectively. The behavior of LS-systems during tabletting was investigated using Kawakita, Heckel, and Leuenberger analysis. LS compacts were examined for P-XRD, DSC, SEM, and in vitro drug dissolution. For optimization, a 32 full factorial design was utilized. Cell line A498 was utilized for in vitro cytotoxicity study. A bioavailability study was performed using rabbits. DSC and P-XRD analysis confirmed the transition of crystalline AXT to its partial amorphization and molecular dispersion. Consequently, LS6 demonstrated a significantly rapid drug dissolution (Q20; >99 %) than the directly compressed tablets (18.05 %). Additionally, 2.03-fold increase in oral bioavailability, and inhibited dose-dependent cell growth with 1.75-fold increased apoptosis rate. Overall, an LS6 compact consisting of 15 % AXT concentration in PEG 200 and a 20 w/w ratio of Fujicalin SG: Aerosil 200 exhibited improved formulation properties, enhanced dissolution rate, and bioavailability. Thus developed potential product may contribute low-cost production with patient-improved survival expectations.

Development of Liquisolid Technology to Overcome Dissolution/Absorption Limitations of Oral Drugs

AbstractIncreasing influx of poorly water-soluble drugs poses a significant challenge to oral drug delivery. Conventional solubilization techniques such as solid dispersion and cyclodextrin inclusion, while capable of improving drug dissolution, suffer from a great predicament in subsequent formulation processing. A novel “powder solution technology,” the liquisolid technique, has come to the forefront in dealing with drug solubilization and formulation of oral “problem” drugs. The liquisolid technique involves the adsorption of liquid medications onto suitable carrier and coating materials, followed by conversion into free-flowing, dry-looking, and compressible powders. In the liquisolid system, the drug is dispersed in an almost molecular state, which greatly contributes to drug dissolution and absorption. This review aims to present the fundamentals of liquisolid technology and update the concept of liquisolid processing to expand its applications. The trend of modern drug discovery, drug solubilization approaches, application of liquisolid technology in formulation innovation, formulation composition, and design of liquisolid systems were discussed in detail. Special emphasis was placed on the application of liquisolid technology to improve the dissolution and bioavailability of poorly water-soluble drugs. Accumulating evidence shows that the liquisolid technology has immense potential to improve oral delivery and facilitate the secondary development of insoluble drugs.

Formulation and Evaluation of Fast Dissolving Tablets of Oxcarbazepine Using Liquisolid Technology

Formulation and Evaluation of Fast Dissolving Tablets of Oxcarbazepine Using Liquisolid Technology

An Effective Approach to Enhance the Dissolution Profile of Curcumin and Quercetin: Liquisolid Compacts

Background: The drugs categorized under BCS class II and IV are poorly water-soluble, which in turn affects their dissolution and bioavailability. To overcome these limitations, namely, poor solubility and bioavailability, several approaches have been tried so far, like, co-solvency, size reduction or micronization, complexation, adsorption on high surface area carriers, etc. Objective: The present article aims to explore the utilization of the liquisolid technique to improve the dissolution profile of curcumin and quercetin, used as a combination in a solid dosage form. It covers the study of the impact of various carriers employed in liquisolid technology on drug dissolution profiles; Avicel pH 101, Fujicalin and Neusilin were used as carriers in this study. Methods: The solubility of the drugs was evaluated in various non-volatile solvents except water to select the vehicle having maximum solubility. All formulations were then prepared using curcumin and quercetin in a ratio of 2:1 (150 mg curcumin : 75 mg Quercetin), comprising a proportion of 40-60% w/w of the total mass of the formulation and were estimated for post-compression parameters. During the final processing of the liquisolid compacts, the carrier is to coating material ratio was kept consistent, i.e., 20:1. Results: Powder X-ray Diffraction (PXRD) and Fourier Transform Infrared Spectroscopy (FTIR) were utilized to analyze drug-excipient interaction; these studies stated no evidence of any physical or chemical interaction between drug(s) and the excipients. The final product was then evaluated for the liquid adsorption capacity and in vitro release of the drugs as a combination, and it was observed that these two properties were found to be significantly improved in the liquisolid compacts. Conclusion: The outcomes indicated that the combination of Neusilin as the carrier and castor oil as a non-volatile solvent was the best-performing formulation appropriate for targeting an improved dissolution profile.

Liquisolids: A Modernistic approach in Drug Delivery System

Liquisolid Technology aims to make drug entities more soluble that have low solubility and low permeability, through the cosolvency theory in a reasonably simple setup that doesn't require expensive technology. A non-volatile solvent is used to dissolve a medicine into molecular dispersion, which is then converted into a powder that has the appearance of being dry and is easily compressible. Extrudates are produced from the material by extrusion using an extruder. To create spherical particles known as Pellets, the extrudates are placed beneath the spheronizer. These pellets or granules can be filled in capsules or can be compacted into tablets according to their dose and can be utilized. Various evaluation parameters like Carr`s Index, Angle of Repose, FTIR, etc was studied. Overall, the study demonstrated that the liqui-pellet might improve a liquisolid formulation's poor flowability, which is thought to be a significant development in the concept's commercial viability. The current review aims to unfurl the utilization of liquisolid technology as a potential drug delivery system for BCS class 2 and 3 drugs.

Novel Approaches to Enhance Solubility Medicine

The solubility enhancement of poorly aqueous soluble drugs presents a significant challenge in pharmaceuticalformulation. Liquisolid technology, also known as powdered solution technology, has emerged as a promising approach toenhance the solubility and bioavailability of such drugs. This paper provides a detailed discussion of the novel approachesemployed within the framework of Liquisolid technology to overcome solubility limitations. The study explores the principles,advantages, and applications of Liquisolid technology in drug formulation, highlighting its potential to revolutionize oralmedication delivery. This research aims to investigate the effectiveness of Liquisolid technology in enhancing drug solubility,elucidate its underlying mechanisms, and evaluate its impact on drug dissolution, bioavailability, and therapeutic outcomes. Theobjectives are to review the background and challenges associated with poor solubility of drugs, introduce the concept ofLiquisolid technology and its principles, discuss the advantages and benefits of Liquisolid technology in solubility enhancement,explore the formulation strategies and key components involved in Liquisolid formulations, evaluate the in vitro and in vivoperformance of Liquisolid systems, and identify future research directions and potential applications of Liquisolid technology inpharmaceutical development. Through this comprehensive analysis, the study aims to provide valuable insights into the novelapproaches based on Liquisolid technology for enhancing drug solubility, facilitating the development of effective and efficientdrug delivery systems. Liquisolid technology, a novel approach to solubility enhancement, offers promising advantages overconventional techniques. It involves solubilizing poorly aqueous soluble drugs using surfactants, then incorporating thesesolubilized drugs into a carrier system or powdered solution. The powdered solution facilitates the conversion of the solubilizeddrug into solid residues, which can be further processed into different dosage forms.

Liqui-pellets as a Novel Approach in the Formulation of Oral Solid Products

In dosage form design, rather particular interest is shown towards solid oral products as they are versatile and highly preferred by the pharmaceutical manufacturing industry. To tackle poor dissolution and bioavailability of problematic drugs, liquisolid technology is developed, from which further advances like liqui-pellet's originated. The latter requires lower economic investment than the liquisolid formulation technology. Some limitations in the liquisolid technology are inadequate flowability, compressibility and the inability to manufacture high-dose oral products, which are very difficult to administer. Overall, the liqui-pellets would overcome the inadequate flowability of the liquisolid formulation adding a better drug release ability. These problems can be resolved by employing the liqui-pellets. This review article provides information about liqui-pellets' advantages, the preparation method, factors affecting them and evaluation studies. The main background areas like liquisolid technology, extrusion and spheronization technology are also discussed. The liqui-pellet system is a significant innovation in oral solid drug products.

Novel Technologies for Enhancing Solubility of Poorly water soluble drugs

Solubility is the process of formation of a uniform system, which includes two, parts (solute and Solvent). There are wide varieties of physical and chemical properties that are needed to be considered to determine the solubility for required preparation. Aqueous solubility is one of the key determining factors, lower aqueous solubility leads to issues faced during the studies of newer formulations(1). Many of the newly formulated preparation is practically insoluble in water, which leads to new problems. Numerous techniques are now available in industries to increasing solubility. Methods like particle size reduction, crystal engineering, salt formulation, solid dispersion, use of surfactant, complexation, and many more are used for chemical and physical alteration. Liquisolid technology is a powder solution technology involves the conversion of a poorly water-soluble drug into dry free flowing powder. Excipients play vital role in this novel technology. It also overcome major challenges like bioavailability with low production cost.

Andrographolide Liquisolid using Porous-Starch as the Adsorbent with Enhanced Oral Bioavailability in Rats

Andrographolide (AGL) is the major component of Andrographispaniculata. The poor water solubility and low dissolution strongly affect its oral absorption. Liquisolid technology has been used to improve its dissolution and oral bioavailability. Liquisolid powders of AGL (AGL-LS-PSG) were obtained by firstly dissolving AGL in the mixture of NMP, PEG 6000 and Soluplus®, and solidified by absorption of the blend in porous starch. Angle of repose, Carr index and Hauser ratio presented good powder fluidity and compressibility characteristics of AGL-LS-PSG. The results of optical microscopic observation, PXRD and DSC analysis indicated that AGL has been completely adsorbed in porous starch granules and existed in an amorphous or molecularly dispersing state. AGL-LS-PSG can obviously increase the drug dissolution rate compared to commercial guttate pills and raw drug. In vivo pharmacokinetic behavior of AGL-LS-PSG was investigated following a single oral administration to rats. The Cmax (0.37 ± 0.06 μg mL−1) and AUC0−2h (13.55 ± 2.67 μg h mL−1) of AGL-LS-PSG were evidently increased compared to commercial guttate pills (Cmax = 0.30 ± 0.21 μg mL−1, AUC0–2h = 9.88 ± 3.57 μg h mL−1). This study indicated great potential of liquisolid technology in effectively improving the dissolution and bioavailability of AGL.

The Role of Excipients in Liquisolid Technology

This article gives criteria for choosing excipients in liquisolid technology. Liquisolid technology is applicable for non polar drugs by converting drug solution into dry free flowing powder. Patient compliance is more in oral route of administration .Numerous techniques like solid dispersion, micronisation, lyophilisation co-grinding, co-precipitation,complexation and nanotechnology are used to increase aqueous solubility Solid dispersion having stability issues while micronization and complexation can cause agglomeration. In Nanotechnology, high cost involved in sophicticated instruments. Liquisolid technology is considered to be one of the best technique to to overcome solubility,dissolution and bioavailability. It convert drug solution into dry free flowing powder. This technique is simple manufacturing process with low production cost. In vitro release is enhanced by using this technology. There is significant role of excipients in this novel technique to get effective release of drug. Associated problems of BCS class II and IV is mostly solved in respect to solubility. Especially carrier with high specific surface area gives good results in overcoming all challenges. Carriers such as Lactose, Starch, Avicel pH101,Fujacilin, Neusilin ,each having specific properties in release of drug. Among all mostly used carriers are Avicel, Fujacilin and Neusilin as with highest Specific Surface Area (SSA) than others. PVP and SSG is considered best disintegrating agent as having good swelling property and flow property as Polyvinypyrrolidine can be used in high dose drugs. With large SSA and high adsorptive property Neusilin, Aerosil , PVP as carrier, coating material and disintegrating agent are considered perfect excipients in liquisolid technology.

Combining Liquisolid and Co-grinding Techniques to Enhance the Dissolution Rate of Celecoxib

PurposeThe classic liquisolid technique is used to enhance the dissolution rate of poorly water-soluble drugs, but in some cases, it is impossible to reach the desired dissolution rate using this technique alone. Therefore, a novel approach using a combination of ball milling and liquisolid technology was investigated to improve the dissolution rate for celecoxib.MethodsFirst, celecoxib was dispersed in a liquid vehicle (PEG 200), then ground in a ball mill for 3 h. Other excipients, including PVP, microcrystalline cellulose as the carrier powder, and silica as the coating material, were added to the mortar. Dissolution testing was carried out in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) media. The effects of aging on the hardness and dissolution profile were also studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) was used to identify changes in the crystallinity or complex formation.ResultsThe novel formulations showed a higher dissolution rate than the conventional tablet or classic liquisolid formulations. Aging did not affect the hardness and dissolution profiles of the liquisolid compacts. The DSC and XRD results suggested that the enhanced dissolution rate is not caused by the formation of any complexes and reduction in crystallinity degree may contribute to the dissolution enhancement. The enhanced dissolution rate is attributed to the elevated specific surface area of the drug in the liquisolid state.ConclusionThe results showed that liquisolid technology combined with ball milling is an efficient tool for enhancing the dissolution of poorly water-soluble drugs.

A short review on liquisolid technology in anti-fungal drugs

A short review on liquisolid technology in anti-fungal drugs

A Short Review on Application of Liquisolid Technology

In this paper we have surveyed about formulation and evaluation of Liquisolid formulations and its work in antidiabetics . Mostly poorly water soluble drugs are in research category despite of less dissolution rate and poor bioavailability. Solubility is a vital parameter to develop new formulation as industries faced serious issue regarding the poor aqueous solubility of the drugs. Various methods for solubility enhancement include modifications of the drug, involvement of co-solvents, complexation, salt formation, size reduction. A propitious technique to solve major challenges like solubility, dissolution rate and their bioavailability. This technique can be defined as the conversion of poorly soluble liquid medications into non-adherent, dry, compressible and free flowing powder mixtures with help of excipients. Many anti-diabetic drugs are belonging to BCS Class-II facing challenges like solubility and bioavailability.

Effect of Formulation Parameter on Dissolution Rate of Flurbiprofen Using Liquisolid Compact

Attempts were made to improve solubility and the liquisolid technology dissolving of medication flurbiprofen. Liquisolid pill was developed utilizing transcutol-HP, polyethylene glycol 400, Avecil PH 102 carrier material and Aerosil 200 layer coating material. Suitable excipient amounts were determined to produce liquisolid powder using a mathematical model. On the other hand, flurbiprofen tablet with the identical composition, directly compressed, was manufactured for comparison without the addition of any unvolatile solvent. Both powder combination characterizations and after-compression tablets were evaluated. The pure drug and physical combination, and chosen liquisolid tablets were studied in order to exclude interacting with the differentional scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR).
 The results showed that transcutol is the ideal solvent with a solubility of 260±3.9 mg/ml in flurbiprofen. All formula developed were determined to be flowable within the specified limitations. The transcutol-like liquidsolid tablet formula of 35 percent w/w flurbiprofen and carrier to coating ratio of 10 was the most acceptable for the disintegration time, the tablet weight and other approved tablet characteristics.
 DSC thermographs demonstrated the development of a solid flurbiprofen amorphic solid solution for both the physical blend of the chosen liquisolid system and its tablets. The lack of chemicals interaction in medication and other components of the formula was demonstrated by the retention of all flurbiprofen characteristic peaks in all FTIR spectra. As an option to enhance solubility and dissolve flurbiprofen, which has a poor water solubility, liquisolid tablet has been evaluated.

Investigation into liquisolid system processability based on the SeDeM Expert System approach

Liquisolid systems are emerging formulation approach for poorly soluble drugs, based on adsorption/absorption of drug dispersion and obtaining free-flowing powder with good compressibility. SeDeM Expert System represents a powder processability evaluation method. It may provide additional insight into liquisolid systems critical quality attributes, but the contribution of this approach remains to be explored. The aims of this study were: pellet preparation by combination of liquisolid technology and water granulation/extrusion, evaluation of liquisolid based systems (pellets/admixtures) and investigation into the applicability of SeDeM Expert System in liquisolid systems characterization. Pellets/admixtures were prepared with microcrystalline cellulose as carrier and crospovidone/silicon dioxide as coating agent. Ibuprofen solution in polyethylene glycol 400 was used as liquid phase. After comprehensive sample characterization, experimentally obtained parameters were mathematically transformed and evaluated in the SeDeM Expert System framework.Pellets exhibited low aspect ratio and excellent flowability, despite liquid load up to 52.2%. The investigated liquisolid admixtures exhibited good flowability and faster drug dissolution than pellets. Single pellet crushing test results exhibited strong correlation with compact indentation hardness and may be used as indentation hardness predictor. SeDeM Expert System provides useful insight into liquisolid system processability and comparative evaluation and it may facilitate final solid dosage form development.

Benign prostatic hyperplasia therapy through liquisolid technology composed of polymer-layered nanocomposites based on silicate that contain babassu oil and copaiba oil-resin

In a previous article by our research group, the association of babassu oil (BBS) and copaiba oil-resin (COPA) in a nanosystem was verified as a potential phytotherapic alternative for treatment and prophylaxis of benign prostatic hyperplasia (BPH). Since few studies have examined their association with nanosystems, we developed polymeric nanocomposites of lamellar silicates containing BBS and COPA to potentially enhance their anti-hyperplastic activity through a process that would be amenable to larger scale production. Organoclay-based-nanocomposites were prepared by an intercalation method in a polyethyleneimine (PEI) solution of low or high molar weight polymer and BBS alone or together with COPA, aiming to develop a technology capable of transforming liquid or oily active pharmaceutical ingredients into suitable powders for compression. A nanocomposite of Viscogel S7® containing BBS-COPA with low molecular weight PEI, presented the highest intercalation efficiency values of BBS (83.08 ± 0.10%) and COPA (70.14 ± 0.88%) along with the highest values of basal spacing (22.12 ± 0.87 Å) and the nanocomposite presented particle diameter suitable for obtaining compactable solids. The produced tablets presented an average weight and hardness within established limits and a rapid dissolution profile in simulated gastric and enteric fluids for both oils. The anti-hyperplasic effect of the BBS-COPA-nanocomposite led to a reduction of the prostate weight (4.53 ± 2.07%), which was similar to results obtained with Finasteride (5.23 ± 2.09%). The histopathological patterns of prostrates from animals treated with the nanocomposite closely matched those observed with control animals. In conclusion, the newly developed nanosystem showed promising potential to reduce the pathological process of BPH and could serve as a natural alternative for treatment.

Producing High-Dose Liqui-Tablet (Ketoprofen 100 mg) for Enhanced Drug Release Using Novel Liqui-Mass Technology

PurposeLiqui-Tablet is a dosage form derived from Liqui-Mass technology. It has proven to be a promising approach to improve drug dissolution rate of poorly water-soluble drugs. So far, Liqui-Tablet is feasible for low-dose drugs. In this study, an attempt was made to produce high-dose Liqui-Tablet, whilst maintaining ideal physicochemical properties for ease of manufacturing.MethodsLiqui-Tablets containing 100 mg of ketoprofen were produced using various liquid vehicles including PEG 200, Span 80, Kolliphor EL, PG, and Tween 85. Investigations that were carried out included saturation solubility test, dissolution test, tomographic study, and typical quality control tests for assessing flowability, particle size distribution, friability, and tablet hardness.ResultsThe weight of these Liqui-Tablets was acceptable for swallowing (483.8 mg), and the saturation solubility test showed PEG 200 to be the most suitable liquid vehicle (493 mg/mL). Tests investigating physicochemical properties such as flowability, particle size distribution, friability, and tablet hardness have shown no issue concerning quality control and manufacturability. The drug release test of the best formulation has shown extremely rapid drug release at pH 7.4 (100% after 5 min). At pH 1.2 the drug release was reasonable considering the formulation was yet to be optimized.ConclusionDespite the high amount of API and liquid vehicle, it is possible to produce a high-dose dosage form with acceptable size and weight for swallowing using the novel Liqui-Mass technology. This has the potential to diversify the technology by removing the restriction of high dose drug that has been seen in liquisolid technology.

Controlling atorvastatin release from liquisolid systems

Liquisolid technology as a novel technique to control the release rate of drugs has attracted the attention of many researchers. This study aims to investigate parameters controlling the drug release from liquisolid formulations. Factors such as the ratio of drug: liquid vehicle, the ratio of edudragit: avicel and the concentration of coating material in the formulations were investigated. All liquisolid compacts were subjected to dissolution testing for 8 hours at 50 rpm in a 900 ml phosphate buffer and temperature of 37 °C. The results showed that adding avicel to liquisolid formulations containing eudragit, not only increased the mechanical strength of the resultant liquisolid tablets but also reduced the drug release significantly. The results showed that the type of liquid vehicle used to dissolved/dispersed the drug was capable of modulating the drug release rate through the capability of solvents to solubilize the drug in liquisolid compacts. Results also showed that a reduction in the pH of the dissolution medium decreased the release rate significantly. It was interesting to note that the volume of the dissolution medium had no significant impact on the drug release rate. FTIR results ruled out any interaction between the drug and other components of the liquisolid formulations. The DSC traces showed that the drug was in an amorphous state in liquisolid formulations. It is concluded from the current study that the type of liquid vehicle, the amount of liquid vehicle and carrier can modulate the drug release from liqusolid compacts.

A Technical Approach of Solubility Enhancement of Poorly Soluble Drugs: Liquisolid Technique.

Solubility is one of the significant pre-formulation properties which regulate the desired concentration of drug in the systemic circulation. Most of the newly discovered chemical entities show poor solubility which consequently leads to poor bioavailability. To enhance the bioavailability of such type of drugs is a big challenge for pharmaceutical scientists. Liquisolid technology is a new and advanced technology used to transform the liquid medication into dry, free-flowing and easily compressible dosage form incorporation with the carrier and coating material. This review represents the technical perspective of Liquisolid technologies that overcome the demerits of classic formulation strategies and amend the bioavailability of the poorly soluble drug. This technique is also approaches the stability, hygroscopicity and agglomeration issue which are mainly occurring in other techniques for solubility enhancement. Several technologies have been utilized to minimize the solubility problem but due to the complicated and expensive machinery fails to achieve the desired bioavailability of the poorly soluble drugs. Therefore, Liquisolid technology has been introduced as an innovative and promising technique that recovers the demerits of classic formulation strategies and also improves the bioavailability of the poorly soluble drug. This article exhibits the technical approach of the liquisolid system by improving the solubility as well as bioavailability of water-insoluble drugs.

An Investigation into the Influence of Process Parameters and Formulation Variables on Compaction Properties of Liquisolid Systems.

Liquisolid technology, as a promising approach for bioavailability enhancement, has received increasing attention in recent years. However, literature reports addressing the challenges for its industrial application, particularly those related to compaction behavior of liquisolid systems, are scarce. The aim of this study was to investigate the influence of process parameters and formulation variables on the flowability, wetting, and compaction properties of the liquisolid systems prepared in a fluid bed processor. The experiments with microcrystalline cellulose, as a carrier, were performed according to 23 full factorial design. The effects of liquid content, spray air pressure, and liquid feed rate on the properties of liquisolid systems were investigated. Liquisolid admixtures with microcrystalline cellulose were compared with those prepared with novel carriers, Fujicalin® and Neusilin® US2. "Out-die" Heckel, modified Walker, and Kuentz-Leuenberger models were used to analyze the compressibility of liquisolid admixtures. The results obtained showed that an increase in liquid content (in the range of 10 to 15%) led to a decrease in flowability of liquisolid admixtures with microcrystalline cellulose, as well as more pronounced influence of spraying conditions. On the other hand, higher liquid content led to higher compressibility. Fujicalin® and Neusilin® US2 liquisolid admixtures were found to have superior flowability and compressibility in comparison with those with microcrystalline cellulose, despite the considerably higher liquid load (50-55% liquid content in Neusilin® US2 compacts). Acceptable compactibility of the investigated liquisolid systems was observed. The fluid bed processor was shown to be suitable equipment for production of liquisolid systems, but with careful adjustment of process parameters.