Poor Water Soluble Drugs Research Articles

Development and Evaluation of Micro Emulsion Formulations of Nebivolol for Solubility Enhancement

Nebivolol HCl is a newer drug of β1-adrenergic blocker category, basically used as anti-hypertensive. It is a 3rd generation, antagonist, having NO (nitric oxide) enhancing vasodilator properties. It has 12% oral bioavailability, because of its pre systemic metabolism by the means of cytochrome P450 2D6 enzymes. Its log P value is 4.03 and 5mg is its daily dose. It is highly lipophilic drug and belongs to class BCS II, with slow dissolution. Bioavailability of any drug can be improved by avoiding its first pass metabolism and promoting solubility. Several researchers have worked on the development of ME formulations on different poor water-soluble drugs, to increase their solubility. The purpose of this study is an attempt to enhance the solubility to improve the bioavailability of nebivolol drug by developing a novel delivery system that is microemulsion (ME) .ME formulations were developed using different oil, surfactant and co-surfactants in different ratio and studied on various parameters. Different preformulation tests done on received sample of Nebivolol. FTIR study was performed in order to find out any interactions between the ingredients. Based on the solubility Capmul Pg-12 was finalized oil, Tween 80 as surfactant, propylene glycol as the cosurfactant based on solubility and emulsification efficiency. Five Nebivolol ME formulations were successfully developed by use of oil, water, SA and Co-SA different ratio. Prepared formulations were studied for different properties- transmittance (%), pH, refractive index, viscosity, drug content, and solubility. It was seen that after 4 hours of diffusion, the drug released from the formulation ME5 is faster and more than that of the other i.e., 90.2±0.06%. It was found that ME5 was more stable and Soluble than other prepared formulations. With the better solubilty the bioavailability of Nebivolol will increased and helps in faster absorption and High diffusion in systemic circulation with lower or no risk of degradation. It somehow also reduced frequent intake of drug.
 Keywords: Nebivolol, micro emulsion, Ternary phase diagram, surfactant, co-surfactant.

Loading drugs into liposomes by temperature up-down cycle procedure with controllable results fitting prediction by mathematical and thermodynamic process

Liposomes are a useful carrier for delivering drugs but rarely make a poorly water-soluble drug (PWSD) realize its therapeutic potential. A key barrier lies in that, by conventional methods, PWSD is mainly loaded just in liposome bilayer membranes, which rarely provide sufficient room to accommodate drugs satisfying clinical therapy. In this investigation, a novel procedure of temperature up-down cycle (TUDC) was developed for loading PWSDs into the liposome interiors instead of bilayer membranes to hold enough agents. In particular, the TUDC procedure renders PWSDs such as curcumin (Cur) entrapment purposely controllable, as evidenced by the encapsulation efficiency (EE) of Cur varies nearly from 0% to 100% in response to changes the determinant factors of the procedure. In addition, several mathematical equations that could calculate the loading efficiency by TUDC were established and proved, when combined with thermodynamic process, able to successfully predict the loading results through including thermodynamic parameters, such as temperature and deduced drug solubility, thus remarkably cutting down the laborious experiments and enhancing liposome development efficiency. Cryo-TEM, SAXS, XRD and DSC tests proved that TUDC is feasible to load a PWSD into PEG-liposomes but rendering the drug in the amorphous state. Thus, the novel TUDC procedure and the established mathematical and thermodynamic process may provide a useful tool to promote the development of liposome products.

A Comprehensive report on Solid Dispersions by Factorial Design

The drugs of present use are lipophilic. Hence there is a need to surge the solubility of these drugs. To encounter this necessity one of the approaches is the formulation of drugs in form of Solid dispersions. Solid dispersions are a type of dispersion having one or extra one API in a torpid carrier at a solid state. We focused on the importance of solid dispersions in pharmaceutical formulation by using factorial design as it was easy to formulate. These solid dispersions are organized by several practises such as solvent technique, supercritical fluid technique and kneading tactic, etc., by referring the several journals, literature and pharmacy magazines we came to know that Solid dispersion are used to improve the solubility of the poor water-soluble drugs and also its bioavailability. At last, we conclude that through these Solid dispersions we can boost the Therapeutic efficiency of hydrophobic drugs by achieving greater solubility.

Evaluation of the effect of carrier material on modification of release characteristics of poor water soluble drug from liquisolid compacts.

Liquisolid compact is a novel dosage form in which a liquid medication (liquid drug, drug solution/dispersion in non-volatile solvent/solvent system) is converted to a dry, free flowing powder and compressed. Objective of the study was to elucidate the effect of carrier material on release characteristics of clopidogrel from liquisolid compacts. Different formulations of liquisolid compacts were developed using microcrystalline cellulose, starch maize, polyvinyl pyrollidone and hydroxypropyl methylcellulose as carrier material in three concentrations (40, 30 and 20%, w/w). Liquid vehicle was selected on the basis of solubility of clopidogrel. Colloidal silicondioxide was used as coating material and ratio of carrier to coating material was kept 10. A control formulation comprised of microcrystalline cellulose (diluents), tabletose-80 (diluents), primojel (disintegrant) and magnesium stearate (lubricant) was prepared by direct compression technique and was used for comparison. All the formulations were evaluated at pre and post compression level. Acid solubility profile showed higher solubility in HCl buffer pH2 (296.89±3.49 μg/mL). Mixture of propylene glycol and water (2:1, v/v) was selected as liquid vehicle. Drug content was in the range of 99–101% of the claimed quantity. All the formulations showed better mechanical strength and their friability was within the official limits (<1%). Microcrystalline cellulose and starch maize resulted in faster drug release while polyvinyl pyrollidone and HPMC resulted in sustaining drug release by gel formation. It is concluded from results that both fast release and sustained release of clopidogrel can be achieved by proper selection of carrier material.

Mutual Effects of Hydrogen Bonding and Polymer Hydrophobicity on Ibuprofen Crystal Inhibition in Solid Dispersions with Poly(N-vinyl pyrrolidone) and Poly(2-oxazolines).

Poly(N-vinyl pyrrolidone) (PVP), poly(2-methyl-2-oxazoline) (PMOZ), poly(2-ethyl-2-oxazoline) (PEOZ), poly(2-n-propyl-2-oxazoline) (PnPOZ), and poly(2-isopropyl-2-oxazoline) (PiPOZ) were used to prepare solid dispersions with ibuprofen (IB), a model poorly-water soluble drug. Dispersions, prepared by solvent evaporation, were investigated using powder X-ray diffractometry, differential scanning calorimetry, and FTIR spectroscopy; hydrogen bonds formed between IB and all polymers in solid dispersions. PMOZ, the most hydrophilic polymer, showed the poorest ability to reduce or inhibit the crystallinity of IB. In contrast, the more hydrophobic polymers PVP, PEOZ, PnPOZ, and PiPOZ provided greater but similar abilities to reduce IB crystallinity, despite the differing polymer hydrophobicity and that PiPOZ is semi-crystalline. These results indicate that crystallinity disruption is predominantly due to hydrogen bonding between the drug molecules and the polymer. However, carrier properties affected drug dissolution, where PnPOZ exhibited lower critical solution temperature that inhibited the release of IB, whereas drug release from other systems was consistent with the degree of ibuprofen crystallinity within the dispersions.

Formulation Development and Evaluation of Liposphere of Poor Water Soluble Drug for Hyperlipidemia

Lipospheres offer a new approach to improve an aqueous solubility of BCS class-II drugs. Simvastatin is a third generation fibric acid derivative belonging to this class, employed clinically as a hypolipidemic agent to lessen the risk caused by atherosclerosis. An attempt was made to improve aqueous solubility of Simvastatin by aid of stearic acid and Paraffin oil. The factorial batches of the Simvastatin lipospheres were formulated by melt dispersion technique using 32 factorial design with variables X1- concentration of stearic acid and X2- concentration of paraffin oil and responses Y1 - % Drug Entrapment (% DE) and Y2 - % Drug Release (% DR). From the surface response graphs the optimized batch was formulated and evaluated for saturation solubility, in-vitro drug release studies. Significant improvement in the aqueous solubility of the drug in the Simvastatin lipospheres supports the applicability of lipospheres as a tool for improving aqueous solubility of the BCS class-II drugs.&#x0D; Keywords: Linospheres; Simvastatin; Drug release; Hyperlipidemic; Drug entrapment.

Effect of Surface Property on the Release and Oral Absorption of Solid Sirolimus-Containing Self-microemulsifying Drug Delivery System.

The combination of self-microemulsifying drug delivery system (SMEDDS) and mesoporous silica materials favors the oral delivery of poorly water-soluble drugs (PWSD). However, the influence of the surface property of the mesopores towards the drug release and in vivo pharmacokinetics is still unknown. In this study, SBA-15 with hydroxyl groups (SBA-15-H), methyl groups (SBA-15-M), amino groups (SBA-15-A), or carboxyl groups (SBA-15-C) was combined with SMEDDS containing sirolimus (SRL). The diffusion and self-emulsifying of SMEDDS greatly improved the drug release over the raw SRL and SRL-SBA-15-R (R referred to as the functional groups). Results of drug absorption and X-ray photoelectron spectroscopy (XPS) showed strong hydrogen binding between SRL and the amino groups of SBA-15-A, which hindered the drug release and oral bioavailability of SRL-SMEDDS-SBA-15-A. The favorable release of SRL-SMEDDS-SBA-15-C (91.31 ± 0.57%) and SRL-SMEDDS-SBA-15-M (91.76 ± 3.72%) contributed to enhancing the maximum blood concentration (Cmax) and the area under the concentration-time curve (AUC0→48). In conclusion, the release of SRL-SMEDDS-SBA-15-R was determined by the surface affinity of the SBA-15-R and the interaction between the SRL molecules and the surface of SBA-15-R. This study suggested that the SMEDDS-SBA-15 was a favorable carrier for PWSD, and the surface property of the mesopores should be considered for the optimization of the SMEDDS-SBA-15.

10122 Development of an In Vitro in Vivo Correlation of Itraconazole Spray-Dried Dispersion Tablets

ABSTRACT IMPACT: As the number of poorly water-soluble drugs in development increases, our research will expand on the science behind improving drug solubility and absorption and ensuring that promising poorly-water solubility drugs do not fail drug development. OBJECTIVES/GOALS: Spray-dried dispersion (SDD) tablet formulation is an approach to increase oral drug solubility and absorption. Methods to predict SDD performance in humans are poorly developed. We aim to develop an in vivo in vitro correlation (IVIVC) between in vitro dissolution and in vivo absorption of itraconazole SDD tablets. METHODS/STUDY POPULATION: This research project involves tablet manufacturing, in vitro dissolution experiments, and a clinical study. We manufactured fast-, medium-, and slow-release SDD tablets containing amorphous solid dispersion of itraconazole (100 mg) and different grades of the polymer hypromellose acetate succinate (HPMC-AS). Tablets differed in slug pressure, tablet compression force, and formulation composition. Dissolution studies were performed using the United States Pharmacopeia (USP) type II apparatus. The clinical study is an ongoing randomized, cross-over, open-label, fasted, single-dose trial in healthy participants (n=12). An IVIVC will be created by comparing the rank order of drug in vitro dissolution with in vivo absorption. RESULTS/ANTICIPATED RESULTS: Tablet manufacturing was successful, and the tablets displayed the same dissolution rate ranking order as anticipated. Fast-release tablets showed the highest percentage of drug dissolved by 10 min (74%) compared to medium- (62%) and slow-release (1.2%) tablets. Percentage drug dissolved differs by at least 10% at all time points among the different release-rate tablets. The clinical study is currently ongoing, and we expect that the pharmacokinetic (PK) profiles differ among the different tablets. We predict that the rank order of tablet absorption in humans will agree with the order of drug dissolved observed in the dissolution experiments. DISCUSSION/SIGNIFICANCE OF FINDINGS: Spray-dried dispersions are a formulation method to try to improve drug solubility and oral drug absorption. This research will elucidate manufacturing parameters that can impact tablet performance and expand on the ability of in vitro dissolution to predict human PK and streamline drug development of poorly soluble drug candidates.

Self-Assembled Micelles of Amphiphilic PEGylated Drugs for Cancer Treatment.

Generally, poor solubility and imprecise delivery of chemotherapeutic drugs can compromise their efficacies for clinical cancer treatment. In order to address such concerns, poor water-soluble drugs are conjugated with poly(ethylene glycol) (PEG) to obtain PEGylated drugs, which have improved water solubility and can also self-assemble in an aqueous solution to form micelles (PEGylated drug micelles). The surface PEG layer enhances the micelles' colloidal stability and reduces the interaction with physiological surroundings. Meanwhile, PEGylated drug micelles are tumor- targeting via the enhanced permeation and retention (EPR) effect to improve antitumor efficacy in comparison with free drugs. PEGylated drug micelles employ drugs as parts of the carrier medium, which increases the micelles' drug loading capacity relatively. The development of stimuli- responsive PEGylated drug micelles facilitates the drug release to be smart and controllable. Moreover, the PEGylated drug micelles show great potentials in overcoming the challenges of cancer therapy, such as multidrug resistance (MDR), angiogenesis, immunosuppression, and so on. In this review, we highlight the research progresses of PEGylated drug micelles, including the structures and properties, smart stimuli-responsive PEGylated drug micelles, and the challenges that have been overcome by PEGylated drug micelles.

Study the structure and thermal properties of carboxymethylated-β-cyclodextrin inclusion complex with bifonazole

Recently, many technological methods of enhancing the solubility and dissolution characteristics of poorly water soluble drugs have been reported in the literature. Сyclodextrins are able to form water-soluble non-covalent inclusion complexes with many poorly soluble lipophilic drugs. The purpose of this study is to evaluate the possibility of interaction of the antifungal drug Bifonazole (BFZ) through complexation with carboxymethylated-β-cyclodextrin (КМ-β-CD). Based on the data obtained, we can conclude that the presence of KM-β-CD improves solubilization of BFZ more than 50 times. Кеуwords: cyclodextrins, solubility, poorly-water soluble drugs, bifonazole.

Solid Dispersion as a Novel approach in Pharmaceuticals

To improve the dissolution rate and bioavailability of poor water soluble drugs, solid dispersion is an effective way. There are also many other methods but solid dispersion method emerged out promising in context to improving solubility of the drug. Generally, the hydrophilic matrix and a hydrophobic drug constitutes the group of solid products that forms solid dispersion. This review article focuses on the preparation methods, solubility enhancement, evaluation parameters, carriers used, limitations, advantages , disadvantages and applications of solid dispersions. This article also focuses the market based products of solid dispersion.

Optimization, physicochemical characterization, and antimicrobial activity of a novel simvastatin nano-niosomal gel against E. coli and S. aureus

Niosomes, as a kind of drug delivery system, is widely used for the topical delivery of lipophilic drugs. Optimization of niosomes plays an essential role in enhancing their therapeutic efficiencies. This study aims to prepare an optimized niosomal formulation of simvastatin (nSIM), a lipophilic member of statins, through the experiment (Response Surface methodology). Optimized niosomes were characterized in size, polydispersity index (PDI), entrapment efficiency (EE), stability, releasing pattern, and antimicrobial activity. The different molar ratio of surfactant and cholesterol were applied to prepare various formulation of simvastatin loaded niosome. Mean particle size and size distribution were analyzed by dynamic light scattering. Antibacterial activity was determined by MIC and MBC tests against Staphylococcus aureus and Escherichia coli. The release rate of simvastatin from noisome nanoparticles was studied by the Franz diffusion cell method. The release pattern was studied through zero order, first order, Higuchi, Korsmeyer-Peppas, and Hixson-Crowell kinetics models. Optimized niosomes were obtained by span 80, drug to cholesterol ratio of 0.4 with 7 min sonication time. Mean particle size, PDI, zeta potential, and entrapment efficiency (EE%) of optimized nSIM were obtained about 168 nm, 0.34, -32.40, and 96 %, respectively. The niosomes significantly decreased the drug's releasing rate and enhanced antibacterial activity against S. aureus and E. Coli. It was found that the release pattern of drug followed the Higuchi kinetic model which means drug release is by diffusion. Overall, our findings indicated that the prepared simvastatin loaded niosomes showed good stability and biological properties than free drug. Our study suggests that niosomal formulation could be considered as a promising strategy for the delivery of poor water-soluble drugs that enhance antibacterial activity.

Development and Characterization of Mucoadhesive Buccal Gel Containing Lipid Nanoparticles of Triamcinolone Acetonide

Abstract: Background: Triamcinolone Acetonide is a synthetic glucocorticosteroid which has been used for its immunosuppressive and anti-inflammatory activity belonging to BCS class IV, yet it is not recommended to be used at higher doses due to its possible adverse effects. Lipid nanoparticle systems are good carriers for poor water soluble drugs, improve permeability and show sustained drug release. Materials and Methods: Triamcinolone Actinide was formulated as Nanostructured Lipid Carriers. High shear homogenization followed by ultra-sonication method was used with Precirol ATO 5 and Isopropyl myristate as lipids. Optimisation was based on their particle size and entrapment efficiency using the design expert software. Conclusion:Formulations F-5 and F-7 were selected as optimised formulations and had drug release patterns that fit Korsmeyer-peppas model kinetics. SEM and TEM studies showed that the Nano structured lipid carriers had size within the nanometre range and morphology resembling type II (amorphous type). The mucoadhesive gel of optimised formulations F-5 and F-7 were prepared as a 1% w/w hydrogel with carbopol 934. These gels showed pseudoplastic fluid nature and good physical properties and also showed a more sustained drug release in comparison to gel incorporated drug suspension. Conclusion: Based on the results obtained it was concluded that Triamcinolone Actinide can be successfully formulated as a gel incorporated with Nanostructured lipid carriers for treatment of buccal diseases. Key words: Triamcinolone Acetonide, Nanostructured lipid carriers, Mucoadhesive buccal gel, Factorial Design, Response Surface plot.

Enhanced Water Solubility and Oral Bioavailability of Paclitaxel Crystal Powders through an Innovative Antisolvent Precipitation Process: Antisolvent Crystallization Using Ionic Liquids as Solvent.

Paclitaxel (PTX) is a poor water-soluble antineoplastic drug with significant antitumor activity. However, its low bioavailability is a major obstacle for its biomedical applications. Thus, this experiment is designed to prepare PTX crystal powders through an antisolvent precipitation process using 1-hexyl-3-methylimidazolium bromide (HMImBr) as solvent and water as an antisolvent. The factors influencing saturation solubility of PTX crystal powders in water in water were optimized using a single-factor design. The optimum conditions for the antisolvent precipitation process were as follows: 50 mg/mL concentration of the PTX solution, 25 °C temperature, and 1:7 solvent-to-antisolvent ratio. The PTX crystal powders were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, high-performance liquid chromatography–mass spectrometry, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Raman spectroscopy, solid-state nuclear magnetic resonance, and dissolution and oral bioavailability studies. Results showed that the chemical structure of PTX crystal powders were unchanged; however, precipitation of the crystalline structure changed. The dissolution test showed that the dissolution rate and solubility of PTX crystal powders were nearly 3.21-folds higher compared to raw PTX in water, and 1.27 times higher in artificial gastric juice. Meanwhile, the bioavailability of PTX crystal increased 10.88 times than raw PTX. These results suggested that PTX crystal powders might have potential value to become a new oral PTX formulation with high bioavailability.

Development of L-Lysine Amino Acid-Based Co-Crystal of Telmisartan Using Crystal Engineering Approach to Improve Solubility, Dissolution, and Micrometric Properties.

To develop a co-crytsal of Telmisartan for enhancing its solubility in water. Intermolecular interaction happens in crystal packing; it utilizes and helps to understand the design of new solid with their respective chemical and physical properties called crystal engineering. It is a blueprint of molecular solids with specific chemical and physical properties through an understanding and handling of intermolecular interaction for increasing the solubility, in case of poor water-soluble drugs. The study was taken under consideration with an aim to generate and synthesize a cocrystal form of Telmisartan (TEL) with L-lysine to improve its water solubility, dissolution, and micrometric properties. Using dry grinding technique, solvent evaporation and cooling crystallization, the results revealed a generation of co-crystals with enhanced solubility by liquid drop grinding method. Hence, this process was further explored to investigate various formulations and process parameters that could significantly affect the crystal solubility, dissolution, and micrometric properties. The solubility of TEL co-crystals was enhanced by L-lysine. Further, the optimized batch was subjected to its micrometric evaluation and physiochemical characterization like FT-IR, NMR, PXRD. The result of the micrometric evaluation showed better results as compared to standards. The dissolution studies also showed a better dissolution rate for TEL co-crystal tablets than TEL tablets formulation. Co-crystals of TEL with L-lysine showed better solubility and dissolution rate.

Niosomal delivery of simvastatin to MDA-MB-231 cancer cells

Objective The objective of this study was to use nano-niosomal formulations to deliver simvastatin as a poor-water soluble drug into breast cancer cells. Significance Our study focused on the problem associated with poor water-soluble drugs which have significant biological activity in vivo. Methods Different niosomal formulations of simvastatin were prepared and characterized in terms of morphology, size, encapsulation efficiency (EE), and release kinetic. Antiproliferative activity and the mechanism were assessed by quantitative real-time PCR and flow cytometry. Moreover, confocal microscopy was employed to analyze the cell uptake of simvastatin loaded niosomes to the cancerous cells. Results Size, polydispersity index (PDI), and EE of the best formulation were obtained as 164.8 nm, 0.232, and 97%, respectively. The formulated simvastatin had a spherical shape and showed a slow release profile of the drug after 72 h. Stability data elucidated an increase in mean diameter and PDI which was lower for 4 °C than 25 °C. Confocal microscopy showed the localization of drug loaded niosomes in the cancer cells. The MTT assay revealed both free drug and drug loaded niosomes exhibited a dose-dependent cytotoxicity against breast cancer cells (MDA-MB-231 cells). Flow cytometry and qPCR analysis revealed drug loaded niosomes exert their cytotoxicity on cancerous cells via regulation of apoptotic and anti-apoptotic genes. Conclusion The prepared niosomal simvastatin showed good physicochemical and biological properties than free drug. Our study suggests that niosomal delivery could be considered as a promising strategy for the delivery of poor water-soluble drugs to cancer cells.

Improvement of In Vitro Dissolution of the Poor Water-Soluble Amlodipine Drug by Solid Dispersion with Irradiated Polyvinylpyrrolidone.

The aim of this study was to increase both the rates of dissolution and bioavailability of the amlodipine (Amlo) drug. Due to the low cost, high solubility, and amorphous state, polyvinylpyrrolidone (PVP) has been used as a drug carrier in the solid dispersion process. Through applying an irradiation technique, powder of (PVP) is irradiated with six 0–50 kGy irradiation doses. The six irradiated (PVP) samples were characterized using gel permeation chromatography, electron spin resonance, and Fourier transform infrared (FT-IR) spectroscopy. The formulation of six (PVP/Amlo) samples at a ratio of 2:1 wt/wt were characterized using FT-IR spectroscopy and X-ray powder diffraction. In vitro dissolution of (Amlo) drug was assessed in a water solvent at pH 1.2 and pH 7. Results demonstrated that there is a change in the physicochemical properties of irradiated (PVP). FT-IR confirmed that there is an intermolecular H bond between the (Amlo) drug and (PVP) polymer. XRD confirmed that (PVP) changes the crystalline (Amlo) to amorphous amlodipine. Irradiated (PVP) at a dose of 20 kGy released approximately 89% from 40 mg of (Amlo) in 60 s. The in vitro rate of amlodipine dissolution depends on the drug–polymer intermolecular H bond. The rate of (Amlo) dissolution is increased due to the drug–drug intramolecular hydrogen bonding replaced with the drug–polymer intermolecular hydrogen bonding, which reduces the crystal packing. Irradiated (PVP) improved the rate of (Amlo) dissolution compared to unirradiated (PVP).

Influence of polymer addition on the amorphization, dissolution and physical stability of co-amorphous systems.

Co-amorphous systems have been developed to address the solubility challenge of poorly-water soluble drugs. However, the dissolution rate of co-amorphous systems can be too fast in some cases, causing super-saturation, followed by precipitation and thereafter loss of the advantage. In this study, hydroxypropyl methylcellulose (HPMC) was co-formulated at 10% (w/w) with carvedilol-L-aspartic acid (CAR-ASP) co-amorphous systems at CAR to ASP molar ratios of 1:1, 1:1.5 and 1:2. No obvious changes of glass transition temperatures (Tgs) were detected for CAR-ASP 1:1.5-HPMC and CAR-ASP 1:2-HPMC compared to the corresponding co-amorphous systems, whilst CAR-ASP 1:1-HPMC showed an increased Tg (88.9±1.3°C) compared to CAR-ASP 1:1 (80.2±0.9°C). HPMC was involved in the molecular interactions of the CAR-ASP-HPMC systems, but did not disturb ionic interactions between CAR and ASP. Addition of HPMC optimized the dissolution of the CAR-ASP systems by reducing the initial dissolution rate and maintaining super-saturation for a longer period. No negative effect of HPMC addition on physical stability was observed at 25 °C and 40 °C under dry conditions for 7months. Therefore, it appears promising to co-formulate a small amount of polymer with co-amorphous systems to achieve optimized dissolution characteristics while maintaining the desired physical stability.

Self-emulsifying Drug Delivery System Improve Oral Bioavailability: Role of Excipients and Physico-chemical Characterization.

Self-emulsifying drug delivery system (SEDDS) is a kind of solid or liquid formulation composed of drugs, oil, surfactant and cosurfactant. It could form a fine emulsion (micro/nano) in the gastrointestinal tract after oral administration. Later on, the formed emulsion is absorbed through the lymphatic pathway. The oral bioavailability of drugs in SEDDS would be improved for bypassing the first-pass effect of the liver. Therefore, SEDDS has become a vital strategy to increase the oral bioavailability of poor watersoluble drugs. In addition, there is no aqueous phase in SEDDS, thus SEDDS is a homogeneous system, consequently being suitable for large-scale production and more stable than conventional emulsion. However, the role of formulation aspects in the biological property of SEDDS is not fully clear. In order to prepare the satisfying SEDDS to improve oral drug bioavailability, we need to fully understand the various factors that affect the in vivo behavior of SEDDS. In this review, we would explore the role of ingredient (drugs, oils, surfactant and cosurfactant) of SEDDS in increasing oral drug bioavailability. We would also discuss the effect of physicochemical property (particle size and zeta potential) of SEDDS on the oral drug bioavailability enhancement. This review would provide an approach to develop a rational SEDDS to improving oral drug bioavailability. Lay Summary: Self-emulsifying drug-delivery system (SEDDS) has been proven to be promising in ameliorating the oral bioavailability of poor water-soluble drugs. This review highlighted the influence of excipients and physicochemical property of SEDDS on the formation of emulsion and the oral absorption of drugs in the body.

Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions.

Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed. In this work, we present an alternative carrier system for ASDs where a water-soluble and water-insoluble carrier are combined to delay the drug release and thus prevent this onset of precipitation. Poly(2-alkyl-2-oxazoline)s were selected as a polymer platform since the solution properties of this polymer class depend on the length of the alkyl sidechain. Poly(2-ethyl-2-oxazoline) (PEtOx) behaves as a water-soluble polymer at body temperature, while poly(2-n-propyl-2-oxazoline) (PPrOx) and poly(2-sec-butyl-2-oxazoline) (PsecBuOx) are insoluble at body temperature. Since little was known about the polymer’s miscibility behaviour and especially on how the presence of a poorly-water soluble drug impacted their miscibility, a preformulation study was performed. Formulations were investigated with X-ray powder diffraction, differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy. PEtOx/PPrOx appeared to form an immiscible blend based on DSC and this was even more pronounced after heating. The six drugs that were tested in this work did not show any preference for one of the two phases. PEtOx/PsecBuOx on the other hand appeared to be miscible forming a homogeneous blend between the two polymers and the drugs.