Solid Dispersion System Research Articles

Production sustained release dosage forms from deliquescent substances by solid dispersion systems

Introduction. The production of solid dosage forms from hygroscopic substances is a complex technological task. The addition of hygroscopic substances into a polymer matrix allows to reduce their moisture absorption capacity.Aim. Reducing the hygroscopicity of deliquescent substances and obtaining sustained release solid dosage forms by using solid dispersion systems.Materials and methods. Substance: DEAE; excipients: Kollidon® VA 64, Soluplus®, PEG 1500, PEG 6000, PEG 8000, Poloxamer Kolliphor® P 188 and Kolliphor® P 407; reagents: hydrochloric acid, sodium dihydrogen phosphate, potassium hydrogen phosphate. The melt of the components was obtained on a twin-screw laboratory extruder and cast into silicone molds. The resulting solid dosage forms were studied for disintegration in three environments corresponding to the sections of the human gastrointestinal tract.Results and discussion. The active pharmaceutical substance DEAE is characterized as deliquescent substance. The introduction of DEAE into PEG-polymer matrices made it possible to reduce the hygroscopicity of solid dosage forms in the form of bars. The introduction of solubilizers into the melt made it possible to obtain bars with the appropriate organoleptic properties. The release of DEAE from bear- or toroid-shaped bars occurs on average 29–47 % faster than from heart-shaped bars.Conclusion. Compositions based on Soluplus® and Kolliphor® P 407 have proven promising for further development of tiles containing DEAE. In order to create tiles with a slow release, it is recommended to use heart-shaped forms, as they have a smaller surface area.

In vitro and in vivo performance of amorphous solid dispersions of ursolic acid as a function of polymer type and excipient addition.

The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients. The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug. The (UA-choline)-Polyethylcaprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P<.05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P<.05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P<.01). The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs.

Study of technological aspects of manufacture of polymer composite material by centrifugal fiber forming method

The object of the study is the technological aspects of manufacturing the hesperidin polymer composite material by the method of centrifugal fiber formation. This method is considered the basis of a relatively new and cost-effective way of producing solid dispersion systems. Using the centrifugal molding method, it is possible to obtain highly soluble forms of active pharmaceutical ingredients in the form of fibers of various sizes using a wide range of polymeric materials with high speed and low cost due to simple equipment. Due to the innovative design of the centrifugal fiber formation method, it was chosen for the development of solid dispersion systems of the bioflavonoid hesperidin, which has a wide range of different pharmacological properties, but low bioavailability. Solid dispersed systems of hesperidin by the method of centrifugal fiber formation were produced on the basis of a pharmaceutically acceptable polymeric carrier of polyvinylpyrrolidone and mannitol. For the obtained solid dispersed systems, such basic pharmaco-technological characteristics as loss in mass during drying, bulk volume, bulk volume after shrinkage, bulk density, bulk density after shrinkage, compressibility index, Gaussner coefficient were determined. Comprehensive tests of the stability of the studied samples of the solid dispersion system of hesperidin were carried out under the conditions of accelerated tests for 6 months. According to the obtained results, it was established that the developed polymer composite material is stable in the studied conditions, and its conditional shelf life is 2 years. A technological scheme for the production of the hesperidin polymer composite material in the form of solid dispersed systems by the method of centrifugal fiber formation has been developed. In particular, the technological process is described step by step and the critical indicators of quality control of the obtained composite material are determined. The proposed technology can be implemented in modern chemical and pharmaceutical industries. This will contribute to the expansion of the market of highly effective socially oriented medicines.

Validation of the spectrophotometric method for the quantitative determination of nimesulide in solid dispersions systems obtained by centrifugal fiber formation

In order to increase the water solubility of the non-steroidal anti-inflammatory active pharmaceutical ingredient, nimesulide, solid dispersed systems were developed using the innovative technology of centrifugal fiber formation. Accordingly, in order to obtain correct results regarding the degree of increase in the solubility of nimesulide in solid dispersed systems, it is necessary to select a method for determining the quantitative content of the active pharmaceutical ingredient in the developed polymer composites. The aim of the study was to develop and validate a spectrophotometric method for the quantitative determination of nimesulide in solid dispersed systems obtained by centrifugal fiber formation. A small commercially available cotton candy machine «Cotton candy maker» (China) was used to produce solid dispersed systems of nimesulide by the method of centrifugal fiber formation. Spectrophotometric studies were performed using an OPTIZEN POP UV spectrophotometer (Meсasys, South Korea) in quartz glass cuvettes with an optical layer thickness of 1 cm (Agilent, USA). The developed spectrophotometric method for the quantitative determination of nimesulide content in centrifugally formed polymeric solid dispersed systems is based on the qualitative reaction of nimesulide with a 0.1 M sodium hydroxide solution, resulting in the formation of a yellow compound with a maximum optical absorption at 400 nm. The validation characteristics of the proposed method, in particular, specificity, linearity, precision, and robustness, were investigated. It was confirmed that the wavelength of 400 nm is specific for the analysis. It was proved that the method is linear (R2 = 0.999) in the range of nimesulide concentrations 80–120%. The accuracy of the method was confirmed at the level of convergence and reproducibility. When changing the wavelength by ± 2 nm, the standard deviation is 0.12%, which indicates the robustness of the developed method. Thus, it is proved that all the selected validation characteristics of the developed spectrophotometric method for determining the quantitative content of nimesulide in centrifugally formed polymeric solid dispersed systems meet the acceptance criteria, which confirms the validity of the method.

Technology for obtaining a highly soluble dispersion of atorvastatin to increase bioavailability

The technology of formation of solid dispersed systems (SDS) is a technological approach that allows to increase the rate of release and bioavailability of poorly soluble active pharmaceutical ingredients (APIs) that belong to class II and IV of the biopharmaceutical classification system (BCS). Atorvastatin calcium is a class II/IV drug according to BCS, which exhibits low bioavailability due to insufficient dissolution. The aim of the work was to conduct a literature and patent search for promising technologies for obtaining highly soluble SDS for effective use in order to increase the solubility of class II and IV APIs, and to propose methods for obtaining highly soluble SDS based on hydrophilic carriers in combination with the API atorvastatin calcium. The objects of research were atorvastatin calcium (API), macrogol (polyethylene glycol 4000, in the form of a finely dispersed powder). To significantly increase the solubility of Class II and IV APIs, thermogranulation/melt granulation methods were used in a high-speed mixer-granulator with a high shear force, equipped with a heating jacket. The main aspects of promising methods of obtaining highly soluble solid dispersion systems based on hydrophilic carriers in combination with the API atorvastatin calcium have been analyzed. It has been established that thermogranulation/melt granulation can be successfully used to increase the solubility of APIs with a hydrophilic carrier with a melting point of 40–60 °C. When using this method, API solubility is increased due to the formation of a highly soluble dispersion in a high-speed mixer-granulator with a high shear force in combination with a heating jacket, consisting of a hydrophilic carrier and calcium atorvastatin particles and excipients, which, in turn, reduces the risk of degradation of atorvastatin calcium in comparison with wet granulation method. This method makes it possible to obtain, depending on the physical characteristics of hydrophilic carriers, a dosage form with an increased level of dissolution, as well as to increase the shelf life of the medicinal product. It has been established that the use of the thermogranulation/melt granulation method, namely, the technology of centrifugal formation of a highly soluble dispersion based on a hydrophilic carrier with API particles and excipients can become the basis for the development of novel dosage forms, which in turn will lead to an increase in the solubility of class II and IV APIs. Such methods of obtaining can be promising, innovative and economically feasible for the development of modern domestic medicinal products.

Utilizing phospholipid as an amphiphilic carrier for solid dispersion of ambrisentan: formulation and evaluation

ABSTRACT: The partial water solubility of ambrisentan poses a challenge to its oral administration despite being the second oral endothelin A-receptor antagonist approved in the United States. In this study, we aimed to improve ambrisentan’s solubility and bioavailability using an amphiphilic phospholipid carrier. Phospholipids, with their glycerol-bound, phosphorus-containing amphiphilic nature, are known to prolong drug lifespan by facilitating drug penetration across cell membranes through hydrogen bonds or van der Waals interactions. Moreover, phospholipid compounds have been shown to significantly enhance drug solubility, permeability, and bioavailability in various studies. We optimized the ratios of ambrisentan and phospholipid carriers (1:1, 1:3, and 1:5) based on saturation and phase solubility experiments. Solid dispersion was prepared using the solvent evaporation technique. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses confirmed the conversion of ambrisentan from a crystalline to an amorphous form in the solid dispersion. The solubility of ambrisentan in the solid dispersion increased by 13-fold with a 1:5 ratio of ambrisentan to phospholipid carrier. The release profile indicated rapid release of the active substance within the first 15 min, corresponding to the peak phospholipid concentration. Pharmacokinetic studies demonstrated higher bioavailability of the medicine compared to the pure drug. This study suggests that phospholipids can effectively enhance drug solubility and bioavailability in solid dispersion systems.

Development of a solid dispersion system for polyvinyl alcohol nanofibers embedded with silicon dioxide particles via emulsion electrospinning for improved solubility of poorly water-soluble drugs

This study explored the development of solid dispersions of probucol (PBC), a poorly water-soluble drug, embedded within polyvinyl alcohol (PVA) nanofibers at a high concentration (30 %) via emulsion electrospinning. This study addressed the issues of low solubility and dissolution rates of such drugs by examining the incorporation of various types of silica particles—Aerosil 200 (A200), Sylisia 320 (SY320), Aerosil R972, and Sylophobic 100—as additives in oil-in-water emulsions. The results revealed that regardless of their hydrophilic or hydrophobic properties, silica particles preserved the amorphous state of PBC within the nanofibers without altering its crystallinity. Notably, all nanofibers embedded with silica particles demonstrated improved drug solubility compared to those without silica. This suggests that silica plays a role in mitigating the reduced solubility of drugs associated with their higher concentrations. Stability assessments of nanofibers embedded with A200 and SY320 under accelerated conditions revealed that A200 nanofibers preserved drug crystallinity and solubility, thus exhibiting superior storage stability. In contrast, SY320 nanofibers underwent drug crystallization, leading to a decrease in solubility upon storage. In conclusion, this study highlights the potential of silica particles in enhancing the solubility and stability of PBC in PVA nanofibers, suggesting that emulsion electrospinning with suitable silica additives is an effective strategy for developing advanced drug delivery systems for poorly water-soluble drugs.

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies

Ex vivo permeability study and in vitro solubility characterization of oral Canagliflozin self-nanomicellizing solid dispersion using Soluplus® as a nanocarrier

Abstract Background and objective: Self-nanomicellizing solid dispersion SNMSD is a new formulation that combines solid dispersion and nanomicelle strategies; the strategy involves utilizing a suitable carrier that self-assembles into nanomicelles when interacting with gastrointestinal fluids. Canagliflozin, a sodium-glucose cotransporter-2 inhibitor for treating type 2 diabetes, has been linked to poor absorption due to its insolubility in aqueous media. The study aimed to create self-nanomicellizing solid dispersion systems for canagliflozin to overcome its pharmaceutical limitations and improve oral bioavailability. Materials and Methods: Soluplus® was chosen as a nanocarrier to improve canagliflozin solubility after screening several polymers using a phase solubility study. The solvent evaporation method was selected for preparing the solid dispersion. The optimal formula was characterized through ex vivo permeability and in vitro studies. Results: The CFZ-SNMSD formula, with a particle size PS of 60.77±1.00 nm and polydispersity index PDI of 0.06±0.02, has a stable distribution upon dilution to 20-fold with water. The apparent solubility of canagliflozin in the optimized CFZ-SNMSD formula was enhanced by 904.40±4 folds due to amorphization and nanomicellization, as demonstrated by transmission electron microscopy. CFZ-SNMSD formula showed a significant enhancement in dissolution rate compared to the physical mixture and pure drugs. The dissolution efficiency parameter confirms these findings (DE30, CFZ-SNMSD = 77.20% compared to DE30, pure drug = 18.28%). Studies show that canagliflozin’s permeability increases exponentially over time due to Soluplus® dispersibility, solubilization, and glycoprotein inhibitory effect, enhancing bioavailability and overcoming GIT membrane barriers. Conclusions: The study indicates that canagliflozin self-nanomicellizing solid dispersion systems are promising methods for improving the oral bioavailability of canagliflozin medication.

Studies on enhancement of solubility and dissolution properties of Nimodipine by solid dispersion technique

Nimodipine, a member of calcium channel blocker, specifically binds to L-type voltage-gated calcium channels. The maximum solubility of nimodipine was found at pH 1.2 and solubility decreases up to pH 4.0. At a pH 6.0 and higher pH, solubility reduces drastically. Suitable solid dispersion systems of nimodipine with PVP-K30 and maltodextrin were prepared by physical mixture, solvent evaporation and kneading methods at 1:1 and 1:3 drug: carrier. Drug content, saturation solubility, FTIR, and in-vitro dissolution were studied. The drug content was uniform, solubility of the drug increased linearly as a function of the carrier concentration and method. The FTIR studies indicates no chemical interaction between drug and polymer. The DP60 and DE60 values of solid dispersion systems prepared by solvent evaporation and kneading method were significantly higher (P&lt;0.05) when compared to DP60 and DE60 values of physical mixture and pure Nimodipine. The dissolution follows first order model and obeyed Hixson- Crowell’s cube root law.

Polymer Matrix and Manufacturing Methods in Solid Dispersion System for Enhancing Andrographolide Solubility and Absorption: A Systematic Review.

Background: Andrographolide (ADG) has poor aqueous solubility and low bioavailability. This study systematically reviews the use of solid dispersion (SD) techniques to enhance the solubility and absorption of ADG, with a focus on the methods and polymers utilized. Methodology: We searched electronic databases including PubMed, Web of Science, Scopus®, Embase and ScienceDirect Elsevier® up to November 2023 for studies on the solubility or absorption of ADG in SD formulations. Two reviewers independently reviewed the retrieved articles and extracted data using a standardized form and synthesized the data qualitatively. Results: SD significantly improved ADG solubility with up to a 4.7-fold increase and resulted in a decrease in 50% release time (T1/2) to less than 5 min. SD could also improve ADG absorption, as evidenced by higher Cmax and AUC and reduced Tmax. Notably, Soluplus-based SDs showed marked solubility and absorption enhancements. Among the five SD techniques (rotary evaporation, spray drying, hot-melt extrusion, freeze drying and vacuum drying) examined, spray drying emerged as the most effective, enabling a one-step process without the need for post-milling. Conclusions: SD techniques, particularly using Soluplus and spray drying, effectively enhance the solubility and absorption of ADG. This insight is vital for the future development of ADG-SD matrices.

Investigation of acute, sub-chronic toxicity, effects of mangiferin and mangiferin solid dispersion (HPTR) on Triton WR1339-induced hyperlipidemia on Swiss albino mice

Mangiferin is a xanthonoid found in Mango leaves in abundance with many effects as a hypoglycemic, antioxidant, and anti-inflammatory agent, plant metabolite, and so on. However, nowadays, mango leaves are merely a waste product in Vietnam. To take advantage of this valuable medicinal resource, extraction conditions of mangiferin using classical and ultrasound methods were researched, and mangiferin was purified from Cat Chu mango leaves (Mangifera indica L., Anacardiaceae) collected in Dong Thap. Ultrasound-assisted extraction method was conducted with the following conditions and mangiferin was extracted at a percentage of 6.728% with a purity of 91.11%. Purified mangiferin was evaluated using molecular absorption spectroscopy UV-Vis, scanning electron microscopy (SEM), X-ray diffraction (XRD) spectroscopy, simultaneous thermal analysis (STA: TGA/DSC), and dissolution measurement method. To optimize the solubility and permeability of mangiferin, the solid dispersion system (HPTR) was made by the combination of HPMC 6M:mangiferin at the ratio of 1:5. To investigate the acute, sub-chronic toxicity and hypolipidemia effect of HPTR as compared to purified mangiferin, we followed guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD, and used tyloxapol (Triton WR1339, 400 mg/kg, i.p.) to induce hyperlipidemia. Our results indicated that purified mangiferin and HPTR extract showed no acute toxicity and sub-chronic toxicity and has potential as an antihyperlipidemic agent. The HPTR brought about a significant decrease in total cholesterol, triglycerides and LDL-c when compared to mangiferin, however there was no significance between them.

Formulation development, characterization, and evaluation of bedaquiline fumarate – Soluplus® – solid dispersion

Bedaquiline fumarate (BQF) is classified as a BCS class II drug and has poor water solubility and dissolution rate, which ultimately compromises bioavailability. The objective of this study is to improve the biopharmaceutical properties of BQF through a solid dispersion system by using Soluplus®. Two solid dispersion systems were prepared i.e. binary solid dispersion (BSD) and ternary solid dispersion (TSD) where 14.31-fold and 20.43-fold increase in solubility of BQF was observed with BSD and TSD in comparison to BQF. In our previous research work, we explored the BSD and TSD of BQF with a crystalline polymer, poloxamer 188, which showed an increment in the solubility of BQF. In the current research, amorphous Soluplus® polymer was selected to formulate BSD and TSD with BQF and showed higher solubility than poloxamer 188. The various solid and liquid state characterization results confirmed the presence of an amorphous form of BQF inside solid dispersion. The Fourier transform infrared spectroscopy showed no chemical interactions between BQF and polymer. The cellular uptake results demonstrated higher uptake in Caco-2 cell lines. Pharmacokinetic studies showed enhanced solubility and bioavailability of TSDs. Hence, the present research shows a promising formulation strategy for enhancing the biopharmaceutical performance of BQF by increasing its solubility.

Comprehensive Characterization and Comparative Assessment of Carvedilol Solid Dispersions: Insights into Enhanced Bioavailability and Stability Profiles

Carvedilol, a non-selective beta-adrenergic antagonist, poses a challenge in achieving optimal bioavailability due to its poor aqueous solubility. This study aimed to enhance the solubility and dissolution rate of carvedilol through the formulation and evaluation of solid dispersions. Various solid dispersion formulations were prepared using different carriers and methods, including solvent evaporation, fusion, and spray-drying techniques. The prepared formulations were systematically characterized using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) to investigate drug-carrier interactions, solid-state changes, and morphological characteristics. Evaluation of the formulated solid dispersions involved in vitro dissolution studies, solubility enhancement assays, and stability assessments. Dissolution profiles revealed significantly improved drug release rates for the solid dispersion formulations compared to the pure drug. The solubility of carvedilol was notably enhanced in the solid dispersion systems, indicating improved drug dissolution behavior. Stability studies demonstrated the robustness of selected formulations against environmental factors over an extended period. Moreover, pharmacokinetic studies conducted in animal models showcased enhanced bioavailability of carvedilol from the optimized solid dispersion formulation compared to the conventional drug formulation. This comprehensive investigation provides valuable insights into the development of carvedilol solid dispersions, elucidating the influence of formulation variables on drug solubility, dissolution, stability, and ultimately, bioavailability enhancement. The findings underscore the potential of solid dispersion technology as a promising strategy to overcome the solubility challenges associated with carvedilol, paving the way for improved therapeutic efficacy and patient compliance.

Enhancement of the Dissolution and Solubility of Canagliflozin Using Nanodispersion Systems

Background: Self-nanomicellizing solid dispersion is a new formulation that combines the advantages of solid dispersion with nanomicelle methods to increase drug oral bioavailability. The technique employs an appropriate carrier to produce a solid dispersion that self-assembles into nanomicelles when in contact with gastrointestinal fluids, improving medication solubility and absorption. Objective: The study aims to develop a self-nanomicellizing solid dispersion of canagliflozin and compare it to non-nanomicellizing formulations. Methods: The solvent evaporation approach was chosen to create a solid dispersion system with soluplus and poloxamer 407 as carriers. Different canagliflozin-to-carrier ratios were investigated in order to develop nanomicellar systems with improved canagliflozin dissolving characteristics. Solid-state analysis was used to characterize the optimum self-nanomicellizing and non-self-nanomicellizing formulations. Results: The physicochemical tests revealed that canagliflozin's crystalline structure transitioned to an amorphous state in the solid dispersion system of both carriers, as evidenced by powder X-ray diffraction and differential scanning calorimetry. Particle size analysis reveals that only soluplus, in all ratios tested, produces a self-nanomicellizing solid dispersion of canagliflozin, whereas poloxamer 407 does not. Self-nanomicellizing systems incorporating Soluplus had a faster dissolving profile than pure drug and non-self-nanomicellizing formulas. Conclusions: Canagliflozin nanodispersion systems with Soluplus as a carrier may improve solubility, dissolving rate, and bioavailability.

Studies on enhancement of solubility and dissolution properties of rosiglitazone hydrochloride by solid dispersion technique

Rosiglitazone HCl, a member of thiazolidinedione class of antidiabetic agent, improves glycemic control by improving insulin sensitivity. The maximum solubility of rosiglitazone was found at pH 1.2 and solubility decreases up to pH 4.0. At a pH 6.0 and higher pH, solubility reduces drastically. Suitable solid dispersion systems of rosiglitazone with maltodextrin and poloxamer were prepared by solvent evaporation and kneading methods at 1:1 and 1:3 drug: carrier. Drug content, saturation solubility, FTIR, XRD, DSC and In-vitro dissolution were studied. The drug content was uniform, solubility of the drug increased linearly as a function of the carrier concentration and method. The FTIR studies suggest possible interaction at molecular level further justified by XRD and DSC studies. The dissolution study suggests, the increase in drug release was dependent on type of method of preparation. The DP60 and DE60 values were significantly higher (P&lt;0.05) in solid dispersion systems prepared by kneading method when compared to pure rosiglitazone, physical mixture and solvent evaporation method. The dissolution follows first order model and obeyed Hixson- Crowell’s cube root law.

Formulation and characterization of glipizide solid dosage form with enhanced solubility.

Glipizide, a poor water-soluble drug belongs to BCS class II. The proposed work aimed to enhance the solubility of glipizide by preparing solid dispersions, using polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG). Solvent evaporation method was used for the preparation of glipizide solid dispersions. Solid dispersions were prepared in four different drug-to-polymer ratios i.e. 1:1, 1:2, 1:3 and 1:4. Mainly effect of three polymers (PVP K30, PVP K90 and PEG 6000) was evaluated on the solubility and dissolution of glipizide. The in-vitro dissolution of all prepared formulations was performed under pH 6.8 at 37°C using USP type II apparatus. In-vitro dissolution results revealed that the formulations having high concentrations of the polymer showed enhanced solubility. Enhancements in the solubility and rate of dissolution of the drug were noted in solid dispersion formulations compared to the physical blends and pure drug. Solid dispersions containing polyvinyl pyrrolidone exhibited a more favorable pattern of drug release compared to the corresponding solid dispersions with PEG. An increase in the maximum solubility of the drug within the solid dispersion systems was observed in all instances. Two solid dispersion formulations were optimized and formulated into immediate-release tablets, which passed all the pharmacopoeial and non-pharmacopoeial tests. Fourier transformed Infrared (FTIR) spectroscopy X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) were used to indicate drug: polymer interactions in solid state. Analysis of the solid dispersion samples through characterization tests indicated the compatibility between the drug and the polymer.

Physical Characterization, Solubility test, and Dissolution test of the Solid Dispersion System of the Andrographolide-chitosan system for effective treatment against colon cancer

This work aimed to examine how varying concentrations of chitosan affect the physiochemical characteristics, and investigate the solubility and dissolving properties of the solid dispersion system including chitosan and andrographolide. A solid-state dispersion system including andrographolide and chitosan was synthesized using various drug-to-polymer ratios. The obtained data were examined for their morphology, physiological state, medication content, test for solubility, and rate of dissolution. The morphology of the system consists of a solid dispersion of andrographolide and chitosan was found to be spherical based on SEM analysis. The solid dispersion systems had infrared spectra with an absorption profile that closely approximated that of the active ingredient. The differences between DTA and XRD analysis indicated a decrease in both the point of melting and the strength of the crystal. The research found a 1.75-fold rise in the soluble state of the system consisting of solid dispersion of andrographolide and chitosan compared to the solubility of the andrographolide component. Furthermore, the chitosan-andrographolide solid dispersion system exhibited a dissolution rate that was 1.6 times higher compared to that of the pure andrographolide molecule. Increasing the amount of chitosan in the system consisting of a solid dispersion of chitosan-andrographolide resulted in a decrease in the degree of crystallinity as well as the andrographolide melting point. This has a beneficial impact on improving the solubility and dissolving rate of andrographolide. The optimized formulation shows a dose-dependent toxicity against HT29 cell lines.

Enhancing the solubility and dissolution rate of piperine via preparation of piperine–hydroxypropyl methylcellulose 2910 solid dispersion system using freeze-drying method

Context: Piperine is the main secondary metabolite isolated from the family Piperaceae. This biologically active ingredient has many pharmacological effects, though its low water solubility limits its absorption in gastrointestinal fluid. Aims: To improve piperine’s solubility and dissolution rate by incorporating it into a solid dispersion system with the hydrophilic polymer hydroxypropyl methylcellulose (HPMC) 2910 via the freeze-drying method. Methods: Three different piperine:polymer ratios – 1:1, 1:2, and 2:1 (w/w) – were prepared. A physical mixture was also prepared in a 1:1 (w/w) ratio for comparison. The physicochemical properties of the samples were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The solubility and dissolution tests were conducted in distilled water. Results: The solid dispersion characterization indicated a decrease in the melting points and endothermic peaks in the DSC analysis, a decrease in peak intensity in the PXRD patterns, no chemical interactions between active substances and polymers in the FTIR analysis, and significant morphological changes in the SEM analysis. The solubility test revealed the highest increase in piperine solubility (7.88-fold increase) for the 1:2 solid dispersion. Moreover, the 1:2 solid dispersion in the dissolution test led to the greatest amount of dissolved piperine (56.445 ± 1.13%). Conclusions: The piperine–HPMC solid dispersion system improved the solubility and dissolution rate of piperine.

Unlocking the Potential: Synergistic Effects of Solid SNEDDS and Lyophilized Solid Dispersion to Enhance Stability Attributes.

Among lipid-based formulations, self-nanoemulsifying drug delivery systems (SNEDDS) have captured a spotlight, captivating both academia and the pharmaceutical industry. These remarkable formulations offer a valuable option, yet their liquid form presents certain challenges for delivering poorly soluble drugs. Ensuring compatibility with capsule shells, maintaining physical and chemical stability, and understanding their impact on lipolysis remain vital areas of exploration. Therefore, the incorporation of this liquid formulation into a solid dosage form (S-SNEDDS) is compelling and desirable. S-SNEDDSs, prepared by adsorption, enhances formulation stability but retards drug dissolution. This study aims to design drug-free solid S-SNEDDS + solid dispersion (SD) as a novel combination to enhance cinnarizine (CN) stability upon storage while maintaining enhanced drug dissolution. Drug-free liquid SNEDDSs were solidified using Neusilin® US2 at a 1:1 ratio. CN-SDs were prepared using freeze-drying technology. The SDs that were developed underwent characterization using various techniques, including scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). In vitro lipolysis studies were conducted to evaluate the effect of the combined system on the performance of the formulation upon exposure to enzymes within biorelevant media. In agreement with the DSC and XRD results, FTIR confirmed the amorphization of CN within the freeze-dried solid dispersion (FD-SD) systems. The in vitro lipolysis studies showed that the drug-free S-SNEDDS + SD combination was able to maintain a significant portion of the initial CN in solution even in the presence of lipase for up to 30 min. The accelerated stability studies showed that the drug-free S-SNEDDS + SD combination maintained 96% intact CN in an amorphous state and more than 90% release at pH 1.2 for up to 6 months, while the dissolution profile at pH 6.8 showed a significant drop in CN release upon storage. Overall, the developed formulation could be a potential technique to enhance the dissolution of weakly basic drugs that possess challenging stability limitations.