Drug Dissolution Properties Research Articles

Predicting physical stability of ternary amorphous solid dispersions using specific mechanical energy in a hot melt extrusion process

This study focuses on the relationship between drug dissolution properties, physical stability against recrystallization, and specific mechanical energy (SME) from a hot melt extrusion (HME) process of ternary amorphous solid dispersions (ASDs) containing indomethacin (IND), HPMC and mesoporous silica (XDP) prepared using different HME screw condition (the number of kneading zones/rotation speed). The screw condition greatly influenced the amorphous characteristics of the processed material and SME values. The higher SME samples demonstrated a larger parachute effect in dissolution test and reduced the rate of recrystallization upon exposure to elevated temperature/humidity conditions, which can be explained from the enhanced miscibility and interactions of IND/HPMC/XDP. The molecular investigation by solid-state NMR (ssNMR) suggested that higher SME input produced better IND/HPMC miscibility and interaction. Interestingly, XDP showed distinct contacts with IND and HPMC in the high-SME samples. The IND-HPMC interaction is not sufficient to maintain a highly mixed ASD at a high drug load without the assistance of XDP. Therefore, SME is a critical parameter for predicting enhanced dissolution and physical stability of IND in ASDs. Moreover, multi-nuclear and multi-dimensional ssNMR provide mechanistic understanding of molecular properties and bring new perspectives for preparation, analysis, and applications of XDP as a pharmaceutical carrier.

All-atomistic molecular dynamics (AA-MD) studies and pharmacokinetic performance of PAMAM-dendrimer-furosemide delivery systems

Improvement of problematic dissolution and solubility properties of a model drug, furosemide, was investigated for poly(amidoamine) (PAMAM) dendrimer complexes of the drug. Full and half generation dendrimers with amino and ester terminals respectively, were studied. In vitro release performance of these complexes was investigated at drug loads ranging 5–60% using simulated gastric fluids. Full generation dendrimers accommodated higher drug loads, outperformed half-generation complexes, and free drug. Pharmacokinetic studies in rats indicated that the dendrimer complexes markedly improved in the bioavailability of the drug compared to the unformulated drug. The G3.0-PAMAM dendrimer complex showed a two-fold increase in Cmax and a 1.75-fold increase in AUC over the free drug. Additionally, Tmax was shortened from approximately 25 to 20 min. One of the first all-atomistic molecular dynamics (AA-MD) simulation studies was performed to evaluate low-generation dendrimer-drug complexes as well as its pharmacokinetic performance. AA-MD provided insight into the intermolecular interactions that take place between the dendrimer and drug. It is suggested that the dendrimer not only encapsulates the drug, but can also orientate the drug in stabilized dispersion to prevent drug clustering which could impact release and bioavailability negatively. AA-MD can be a useful tool to develop dendrimer-based drug delivery systems.

Permeability of glibenclamide through a PAMPA membrane: The effect of co-amorphization

Co-amorphous systems are an attractive alternative for amorphous solid polymer dispersions in the formulation of poorly soluble drugs. Several studies have revealed that co-amorphous formulations can enhance the dissolution properties of poorly-soluble drugs and stabilize them in the amorphous form. However, the interplay between the drug dissolution rate, drug supersaturation and different co-formers on membrane permeability of the drug for co-amorphous formulations remains unexplored.By using side-by-side chambers, separated by a PAMPA (parallel artificial membrane permeability assay) membrane, we were able to simultaneously test dissolution and passive membrane permeability of the co-amorphous combinations (1:1 molar ratio) of a poorly soluble drug glibenclamide (GBC) in combination with two amino acids, either serine (SER) or arginine (ARG). In addition, a known passive permeability enhancer sodium lauryl sulfate (SLS) was included in the co-amorphous mixtures at two concentration levels. The mixtures were also characterized with respect to their solid-state properties and physical stability.It was found that GBC mixtures with ARG and SLS had superior dissolution and physical stability properties which was attributable to the strong intermolecular interactions formed between GBC and ARG. These formulations also had optimal permeability properties due to their high concentration gradient promoting permeation and possible permeation enhancing effect of the co-formers ARG and SLS. Thus, simultaneous testing of dissolution and permeation through a PAMPA membrane may represent a simple and inexpensive tool for screening the most promising amorphous formulations in further studies.

Chronomodulated drug delivery system of Irbesartan: Formulation and development using Desing of Experiment (DoE)

The work is based on pulsatile principles to deliver a programmed dose of Irbesartan, an angiotensin-II receptor antagonist for chronotherapy of hypertension induced by excessive secretion of aldosterone, thereby lower the blood pressure at early morning. Solid dispersion of Irbesartan, a BCS class II drug, was prepared by using Poloxamer-188 by melt method in ratio of 1:1 to increase the dissolution properties of drug. Compressed coated pulsatile tablets included a core layer consisting of Kyron T-134 as a super-disintegrant and pulsatile layer comprising of HPMC K4M and Eudragit RLPO. The prepared core tablets were evaluated for weight variation, hardness, thickness, friability, drug content, disintegration time and In vitro dissolution studies. Final core tablet (C8) was selected on the basis of disintegration time (23.33 ± 2.08 s). For optimization Face centred central composite design was employed to study the effect of independent variables viz. Weight ratio of HPMC K4M: Eudragit RLPO (X1) and Total weight of coating (X2) on dependent variables viz. Drug release lag time (Y1) and Drug release after lag time within 15 min (D15) (Y2). Results revealed positive influence of independent factors on responses. The data were statistically analyzed using ANOVA and were found to be statistically significant (P < .05). Mathematical modeling for kinetic studies revealed that the release profile after lag time followed first order kinetics. Accelerated stability studies for one month at 40 ± 2 °C/75 ± 5% RH showed no remarkable changes concluding that a successful pulsatile drug delivery system of Irbesartan was developed.

Microwave processed solid dispersions for enhanced dissolution of gemfibrozil using non-ordered mesoporous silica

This study describes the application of three non-ordered mesoporous silicas (Syloid AL-1, Syloid 72 and Syloid 244) in improving the dissolution rate of a poorly aqueous soluble drug, namely gemfibrozil. For this purpose, solid dispersions were formulated using a robust and controlled microwave heating method. Prepared formulations were subjected to solid state characterisation and dissolution behaviour. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results confirmed that microwave heating method incorporated gemfibrozil in an amorphous form in Syloid 72 and Syloid 244. This was attributed to a large pore volume and diameter compared with Syloid AL-1 which has a small pore volume. Presence of more crystalline drug in the case of Syloid AL-1 based formulations was attributed to larger surface area where drug was adsorbed in layers as confirmed by the scanning electron microscopy. DSC and XRD results also confirmed stability of formulations when stored for 3 months under stressed conditions (40°C and 75% RH). FT-IR results show lack of interaction between silica and the drug in all cases. It was also noted that all three silica types improved the dissolution behaviour of gemfibrozil when compared with dissolution properties of pure drug. The surface properties of Syloid 72 were found optimum as it enhanced the rate of dissolution of gemfibrozil from microwave processed formulation far better than physically mixed formulations and those prepared with Syloid AL-1 and Syloid 244.

Formulation of cilostazol spherical agglomerates by crystallo-co-agglomeration technique and optimization using design of experimentation.

Introduction:Spherical agglomeration is one of the novel techniques for improvement of flow and dissolution properties of drugs. Cilostazol is a biopharmaceutics classification system Class II drug with poor solubility resulting in limited bioavailability. The present study aims at improving the solubility and dissolution of cilostazol by crystallo-co-agglomeration technique.Materials and Methods:Cilostazol agglomerates were prepared using various polymers with varying concentration of hydroxypropyl methylcellulose E 50 (HPMC E50), polyvinyl pyrrolidone K30 (PVP K30), and polyethylene glycol 6000. The influence of polymer concentration on spherical agglomerate formation was studied by 32 factorial design. Cilostazol agglomerates were evaluated for percent yield, mean particle size, drug content, aqueous solubility, and in vitro dissolution and further characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD).Results:The agglomeration process resulted in optimized formulation, F3 with mean agglomerate size of 210.0 ± 0.56 μm, excellent flow properties, approximately 15-fold increase in solubility than pure cilostazol and complete drug release in 60 min. Process yield, agglomerate size, and drug release were affected by amount of PVP K 30 and HPMC E50. The presence of drug microcrystal was confirmed by SEM, whereas FTIR study indicated no chemical change. Increase in drug solubility was attributed to change of crystalline drug to amorphous form that is evident in DSC and XRD.Conclusion:Crystallo-co-agglomeration can be adopted as an important approach for increasing the solubility and dissolution of poorly soluble drug.

Composite bi-layered erodible films for potential ocular drug delivery

Bi-layered hydroxypropylmethylcellulose and Eudragit based films were formulated as potential ocular drug delivery systems using chloramphenicol as a model antibiotic. Films were plasticized with polyethylene glycol 400 present in the Eudragit layer or both Eudragit and hydroxypropylmethylcellulose layers, and loaded with chloramphenicol (0.5% w/v in solution) in the hydroxypropylmethylcellulose layer. The weight, thickness and folding endurance of the optimized formulations were measured and further characterised for transparency, tensile, mucoadhesive, swelling and in vitro drug dissolution properties. The physical form of chloramphenicol within the films was evaluated using differential scanning calorimetry (DSC), and X-ray diffraction (XRD), complimented with scanning electron microscopy and energy dispersive X-ray spectroscopy. Fourier transform infrared spectroscopy was used to assess the interactions between the drug and the film components and confirm chloramphenicol’s presence within the sample. Optimum films showed high transparency (≥80% transmittance), ease of peeling from Petri dish and folding endurance above 250. Average thickness was lower than contact lenses (0.4–1mm), confirming them as thin ocular films. The tensile properties showed a good balance between toughness and flexibility, and mucoadhesivity showed that they could potentially adhere to the ocular surface for prolonged periods. The drug loaded films showed swelling capacity that was greater than 300% of their original weight. The physical form of chloramphenicol within the films was amorphous (DSC and XRD) whilst in vitro drug dissolution showed sustained drug release from the films for four hours, before complete erosion. The chloramphenicol loaded films represent a potential means of treating common eye infections.

Liquisolid Technology: A Review

Liquisolid system is a novel concept of drug delivery via oral route. Solubility is the phenomenon of dissolution of solid in liquid phase and is one of the important parameter to achieve desired concentration of drug in systemic circulation for pharmacological response. Poorly water soluble compound's oral administration often require high doses in order to reach therapeutic plasma concentrations because insufficient dissolution rate of the drug is the limiting factor in the oral bioavailability and one of the most challenging aspects of drug development. Design of this technique was according to new mathematical model proposed by Spireas et al. The drug is dissolved or dispersed in suitable non-volatile solvent and this liquid medication is converted to free flow powder by using carrier and coating material. To this suitable excipients were added and tabletting by direct compression. In this case, even though the drug is in a solid dosage form, it is held within the powder substrate in solution or, in a solubilized, almost molecularly dispersed state, which contributes to the enhanced drug dissolution properties. Large scale production of fabricated drug on commercial level. Succesful liquisolid tablet is a determination of optimal flowable liquid retention.

Pharmaceutical Advances in Cyclodextrin Inclusion Complexes for Improved Bioavailability of Poorly-Soluble Drugs

Cyclodextrins (CDs) are commonly used in drug formulations as solubility enhancers because of their ability to form water-soluble inclusion complexes with poorly water-soluble drugs. Cyclodextrins are useful molecular chelating agents. The cyclodextrins have a wide range of applications in different areas of drug delivery and pharmaceutical industry due to their complexation ability and other versatile characteristics. Orally administered drugs completely absorb only when they show fair solubility in gastric medium and such drugs shows good bioavailability. The solubility and dissolution properties of drugs play an important role in the process of formulation development. The most common pharmaceutical application of cyclodextrin is to enhance the solubility, stability, safety and bioavailability of drug molecules. Cyclodextrins are cyclic oligosaccharides which have recently been recognized as useful pharmaceutical excipients. As a result of molecular complexation phenomena CDs are widely used in many industrial products, technologies and analytical methods. The negligible cytotoxic effects of CDs are an important attribute in applications such as drug carrier, food and flavors, cosmetics, packing, textiles, separation processes, environment protection, fermentation and catalysis. The objective of this review is to discuss and summarize some of the findings and applications of cyclodextrin and their derivatives indifferent areas of drug delivery. The paper also highlights important CD application in drug solubility and dissolution, bioavailability, safety and stability, their use as excipients in drug formulation, design of various novel delivery systems like liposome, microspheres, microcapsules, and nanoparticles.

Composite alginate and gelatin based bio-polymeric wafers containing silver sulfadiazine for wound healing

Lyophilized wafers comprising sodium alginate (SA) and gelatin (GE) (0/100, 75/25, 50/50, 25/75, 0/100 SA/GE, respectively) with silver sulfadiazine (SSD, 0.1% w/w) have been developed for potential application on infected chronic wounds. Polymer–drug interactions and physical form were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), respectively, while morphological structure was examined using scanning electron microscopy (SEM). Functional characteristics [(mechanical hardness and adhesion using texture analyzer, and swelling capacity)] of blank wafers were determined in order to select the optimal formulations for drug loading. Finally, the in vitro drug dissolution properties of two selected drug loaded wafers were investigated. There was an increase in hardness and a decrease in mucoadhesion with increasing GE content. FTIR showed hydrogen bonding and electrostatic interaction between carboxyl of SA and amide of GE but no interaction between the polymers and drug was observed, with XRD showing that SSD remained crystalline during gel formulation and freeze–drying. The results suggest that 75/25 SA/GE formulations are the ideal formulations due to their uniformity and optimal mucoadhesivity and hydration. The drug loaded wafers showed controlled release of SSD over a 7h period which is expected to reduce bacterial load within infected wounds.

Influence of the preparation method on the physicochemical properties of indomethacin and methyl-β-cyclodextrin complexes

The main objective of this study was to investigate different manufacturing processes claimed to promote inclusion complexation between indomethacin and cyclodextrins in order to enhance the apparent solubility and dissolution properties of indomethacin. Especially, the effectiveness of supercritical carbon dioxide processing for preparing solid drug–cyclodextrin inclusion complexes was investigated and compared to other preparation methods. The complexes were prepared by physical mixing, co-evaporation, freeze drying from aqueous solution, spray drying and supercritical carbon dioxide processing methods. The prepared complexes were then evaluated by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, solubility and dissolution studies. The method of preparation of the inclusion complexes was shown to influence the physicochemical properties of the formed complexes. Indomethacin exists in a highly crystalline solid form. Physical mixing of indomethacin and methyl-β-cyclodextrin appeared not to reduce the degree of crystallinity of the drug. The co-evaporated and freeze dried complexes had a lower degree of crystallinity than the physical mix; however the lowest degree of crystallinity was achieved in complexes prepared by spray drying and supercritical carbon dioxide processing methods. All systems based on methyl-β-cyclodextrin exhibited better dissolution properties than the drug alone. The greatest improvement in drug dissolution properties was obtained from complexes prepared using supercritical carbon dioxide processing, thereafter by spray drying, freeze drying, co-evaporation and finally by physical mixing.Supercritical carbon dioxide processing is well known as an energy efficient alternative to other pharmaceutical processes and may have application for the preparation of solid-state drug–cyclodextrin inclusion complexes. It is an effective and economic method that allows the formation of solid complexes with a high yield, without the use of organic solvents and problems associated with their residues.

Bioequivalence Assessment of Metformin Tablet Formulations of Bangladesh

Six marketed oral antidiabetic metformin tablets in Bangladesh have been studied for their drug content, release profile and glucose lowering capacities. This sort of study is a good indicator for in vivo evaluation of the quality of an oral antidiabetic preparation. Marketed preparations of metformin-HCl from different manufacturers were randomly chosen for this study. The drug content was within the United State Pharmacopoeia (USP) specified limit (95-105%) in all cases. The blood glucose levels were investigated in streptozotocin-induced diabetic rats (SIDRs) after 5 hours of single dose (110 mg/kg body weight) treatment of the products; significantly (p&lt;0.05) reduced blood glucose level by 58.1, 53.2, 50.8, 77.0, 72.9 and 49.1%, respectively; which were consistent with antihyperglycemic effects of standard metformin-HCl (71.3%). All the products were found to be qualified in lowering blood glucose level. It may be inferred that the metformin-HCl tablets of Bangladeshi manufacturers complies with the standard specifications for drug contents, dissolution and antihyperglycemic properties.© 2014 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: http://dx.doi.org/10.3329/jsr.v6i3.19290 J. Sci. Res. 6 (3), 581-588 (2014)

Electrospinning of diosmin from aqueous solutions for improved dissolution and oral absorption

A nanofibrous membrane carrier for nearly water insoluble drug diosmin was formulated. The aim of this study was to evaluate the drug release and dissolution properties in an aqueous buffer of pH 7.8, and to compare the suitability of the drug carrier with the available drug forms and screen diosmin absorption extent.The membranes were produced from HPC/PVA/PEO-drug water solutions and then evaluated by SEM and DSC measurements. The results showed that diosmin was incorporated within the nanofibers in an amorphous state, and/or as a solid dispersion. The results of in vitro release experiments excerpt a very fast release of the drug, followed by the formation of an over saturated solution and partial precipitation of the drug (a “spring” effect). The enormous increases in dissolution of the drug from a nanofibrous carrier, compared to a micronized and crystalline form, was achieved. The in vivo bioavailability study carried out on rats showed higher initial drug plasma levels and higher AUC values after administration of the nanofibrous drug formulation, compared to the micronized form. The results of the study demonstrated that the improvement of the diosmin in vitro dissolution also brought the enhanced in vivo absorption extent of the drug.

Physico-chemical characterization in solution and in the solid state of clonazepam complexes with native and chemically-modified cyclodextrins

Clonazepam (CLZ) is a benzodiazepine derivative, whose bioavailability, limited by its very poor water-solubility, could be improved by cyclodextrin complexation. However, the choice of the most proper cyclodextrin to use to fully exploit its potential favourable effects on the drug, is a critical step. Therefore, in the present work, the performance of some amorphous cyclodextrin (CD) derivatives in terms of complexing, solubilizing and amorphizing power towards CLZ was carefully evaluated and compared with that of natural CDs. The role of CD cavity size, amorphous or crystalline nature, and presence and type of substituents on its ability in producing effective interactions with the drug has been investigated. Equimolar CLZ–CD solid systems were obtained by blending, kneading, co-grinding and coevaporation. Drug–CD interactions were investigated by phase-solubility analysis, differential scanning calorimetry and X-ray powder diffractometry. Among the natural CDs, β-CD showed the highest complexing ability, suggesting that its cavity size is the most proper to host the drug molecule. The presence of substituents had a negative effect on the performance of α-CD and γ-CD, while it improved the complexing and solubilizing power of β-CD, and the methylated derivative was more effective than the hydroxypropylated one. Solid-state studies revealed that amorphous CDs had highest amorphizing power than the corresponding natural crystalline ones, and methylated-β-CD (Me-β-CD) was the best carrier. As for the preparation method, co-grinding was the most powerful in promoting the formation of efficacious drug–CD solid-state interactions. Dissolution rate studies confirmed Me-β-CD as the best partner for CLZ and co-grinding as the best method for maximizing the drug dissolution properties. Therefore, co-ground products with Me-β-CD could be selected as the best system for future development of CLZ formulations with improved therapeutic efficacy.

SOLUBILITY ENHANCEMENT AND DISSOLUTION IMPROVEMENT- LIQISOLID TECHNIQUE

This technique is based upon the admixture of drug loaded solutions with appropriate carrier and coating materials. The use of non-volatile solvent causes improved wettability and ensures molecular dispersion of drug in the formulation and leads to enhance solubility. By using hydrophobic carriers (non-volatile solvents) one can modify release (sustained release) of drugs by this technique. Liquisolid system is characterized by flow behavior, wettability, powder bed hydrophilicity, saturation solubility, drug content, differential scanning calorimetry, Fourier transform infra red spectroscopy, powder X-ray diffraction, scanning electron microscopy, in-vitro release and in-vivo evaluation. The increased bioavailability is due to either increased surface area of drug available for release, an increased aqueous solubility of the drug, or improved wettability of the drug particles. According to the new formulation method of liqui-solid compacts, liquid medications such as solutions or suspensions of water insoluble drugs in suitable nonvolatile liquid vehicles can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. It has been speculated that such systems exhibit enhanced release profiles. In this case, even though the drug is in a solid dosage form, it is held within the powder substratin solution or, in a solubilized, almost molecularly dispersed state, which contributes to the enhanced drug dissolution properties. According to the new formulation method of liquisolid compacts, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile liquid vehicles can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. Large scale production of fabricated drug on commercial level successful liquisolid tablet is a determination of optimal flowable liquid retention. Keywords: Poorly soluble drugs, coating material, carrier, hydrophilic solvent, liquisolid compacts

Design and development of liquisolid compact of candesartan cilexetil to enhance dissolution

BackgroundCandesartan cilexetil is an angiotensin-II receptor antagonist used for the treatment of hypertension. It is hydrophobic drug which belongs to BCS class II and its half life is 5.1 h with 15–40% bioavailability. Attempt had made to investigate the use of liquisolid technique in improving the dissolution of candesartan cilexetil in a solid dosage form. MethodsThe liquisolid tablets were formulated by using Tween 80, as liquid vehicle, microcrystalline cellulose as a carrier material, silica as a coating material and sodium starch glycolate used as a superdisintegrant. The new mathematical model and 32 full factorial design was utilized to formulate various liquisolid powder systems. Result and discussionAll prepared liquisolid batches were subjected to, weight variation, drug content uniformity, hardness, friability test, disintegration test and dissolution tests. Liquisolid system is also tested for DSC, XRD and IR .All the tested liquisolid tablet formulations showed higher drug dissolution than the conventional, directly compressed tablet. ConclusionDSC and XRD study suggested loss of candesartan cilexetil crystallinity upon liquisolid formulation which was further confirmed by SEM, it indicates that drug is held within the powder substrate in a solubilized, almost molecularly dispersed state, which lead to the enhanced drug dissolution properties.

Novel techniques for solubility, dissolution rate and bioavailability enhancement of class II and IV drugs

Enhancement of solubility, dissolution rate and bioavailability of drug is a very challenging task in drug development, nearly 40% of the new chemical entities currently being discovered are poorly water soluble drugs. The solubility and dissolution properties of drugs play an important role in the process of formulation development. Among all newly discovered chemical entities most of the drugs are lipophilic and fail to reach market due to their poor water solubility. The ability to deliver poorly soluble drugs will grow in significance in the coming years as NCEs are relied upon for a larger share of the revenue within the pharmaceutical market by innovator companies. Similarly, generic drug manufacturers will need to employ economically efficient methods of delivery as more low solubility drugs go off patent, in order to maintain a competitive edge and sufficiently compete as profit margins shrink in this price-sensitive industry.

An investigation on the correlation between drug dissolution properties and the growth behaviour of granules in high shear mixer

The aim of this study was to investigate the correlation between the growth behaviour and in-vitro dissolution rate of water-insoluble drugs prepared with high-shear wet granulation. Granules containing nimodipine, microcrystalline cellulose, low-substituted hydroxypropylcellulose and aqueous solution of hydroxypropylcellulose were prepared and the effects of independent process variables, including impeller speed and liquid-to-solid ratio were taken into consideration. The mean granule size, granule-size distribution (GSD), porosity and surface properties were monitored at different kneading times to identify the granule-growth mechanisms simultaneously. A computer-based method was applied to simulate the dissolution behaviour of polydisperse granules based on the GSD data. The in-vitro dissolution rate of drug was high for the early stages of granulation and sharply decreased when coalescence and consolidation of granules started, approaching a flat and low level when granules were sufficiently consolidated. The simulated dissolution results were in agreement with experimental observations and were significantly affected by the GSD, porosity and surface properties of granules during the granulation process. Moreover the GSD was directly related to the granule-growth behaviour and mechanisms. In general, it was concluded that the dissolution properties of nimodipine basically correlated with the growth behaviour of granules in a high-shear mixer. The simulation method based on GSD can be used as a convenient and rapid way to predict the dissolution properties for formulation development and granulation optimization.

A Method for Improving the Wetting and Dissolution Properties of Hydrophobic Drugs of Low Aqueous Solubility

A Method for Improving the Wetting and Dissolution Properties of Hydrophobic Drugs of Low Aqueous Solubility

Solid dispersions in the form of electrospun core-sheath nanofibers

BackgroundThe objective of this investigation was to develop a new type of solid dispersion in the form of core-sheath nanofibers using coaxial electrospinning for poorly water-soluble drugs. Different functional ingredients can be placed in various parts of core-sheath nanofibers to improve synergistically the dissolution and permeation properties of encapsulated drugs and to enable drugs to exert their actions.MethodsUsing acyclovir as a model drug, polyvinylpyrrolidone as the hydrophilic filament-forming polymer matrix, sodium dodecyl sulfate as a transmembrane enhancer, and sucralose as a sweetener, core-sheath nanofibers were successfully prepared, with the sheath part consisting of polyvinylpyrrolidone, sodium dodecyl sulfate, and sucralose, and the core part composed of polyvinylpyrrolidone and acyclovir.ResultsThe core-sheath nanofibers had an average diameter of 410 ± 94 nm with a uniform structure and smooth surface. Differential scanning calorimetry and x-ray diffraction results demonstrated that acyclovir, sodium dodecyl sulfate, and sucralose were well distributed in the polyvinylpyrrolidone matrix in an amorphous state due to favoring of second-order interactions. In vitro dissolution and permeation studies showed that the core-sheath nanofiber solid dispersions could rapidly release acyclovir within one minute, with an over six-fold increased permeation rate across the sublingual mucosa compared with that of crude acyclovir particles.ConclusionThe study reported here provides an example of the systematic design, preparation, characterization, and application of a novel type of solid dispersion consisting of multiple components and structural characteristics.