Effect of XlogP and hansen solubility parameters on the prediction of small molecule modified docetaxel, doxorubicin and irinotecan conjugates forming stable nanoparticles.

Small molecule-chemotherapeutic drug conjugate nanoparticles (SMCDC NPs) has a great advantage in improving drug loading. However, the factors which influence these conjugates forming stable nanoparticles (NPs) are currently unclear. In our previous studies, we synthesized a series of fatty acid-paclitaxel conjugates and suggested that the changes in the hydrophobic parameters (XlogP), solubility parameters and crystallinity of these fatty acid-paclitaxel conjugates were the key factors for affecting these small molecule-chemotherapeutic drug conjugates (SMCDCs) forming stable NPs in water. Here, we selected clinically widely used chemotherapeutic drug (docetaxel (DTX), doxorubicin (DOX) and irinotecan (Ir)) as model drug, and chose three straight-chain fatty acids (acetic acid (Ac), hexanoic acid (HA) and stearic acid (SA)) and one branched small molecule (N-(tert-butoxycarbonyl) glycine (B-G)) to synthesize 12 SMCDCs. Our results indicated that our prediction criterions obtained from paclitaxel conjugates were also appropriated for these synthesized SMCDCs. We suggested that the present studies expanded the scope of application of the above-mentioned influencing factors, provided research ideas for the rational design of SMCDC forming NPs and a basis for screening NPs with good anticancer activity.

3D printing of immediate-release tablets containing olanzapine by filaments extrusion.

In this work, hot-melt extrusion (HME) is coupled with fused deposition modeling (FDM) mediated 3D printing to demonstrate additive manufacturing to fabricate immediate release (IR) prototypes of olanzapine with the aim of enhanced solubility using a fast disintegrating polymer (Kollicoat® IR). Drug-polymer solubility and interaction parameters were estimated by Hansen solubility parameters and Hildebrand-Scott equation. The obtained values signified drug-polymer miscibility. The detailed in vitro physicochemical evaluations of the developed filament through HME and its derived 3D printed tablet by FDM technique were assessed thoroughly by several analytical means such as light microscopy, DSC, XRD, FT-IR, SEM, etc. The average disintegration time of this developed 3D printed IR tablet was found to be 63.33 (±3.6) sec complying with the USP limit. Additionally, in vitro dissolution study data revealed almost close correlations and both showed 100% of drug release within 15 min, thus complying with the definition of IR tablet. Thus, this study demonstrates the feasibility of directly using olanzapine-Kollicoat® IR through the HME process without the addition of any plasticizers, organic solvents, etc. and coupling of HME with 3D printing technology allowing prototypes of IR tablet of olanzapine.

On-Demand Reversible UV-Triggered Interpenetrating Polymer Network-Based Drug Delivery System Using the Spiropyran-Merocyanine Hydrophobicity Switch.

A reversible switchable on-demand UV-triggered drug delivery system (DDS) based on interpenetrating polymer networks (IPNs) with silicone as the host polymer and spiropyran (SP)-functionalized guest polymer is designed and demonstrated. The photo-responsive IPNs provide a new triggered drug delivery concept as they exploit the change in intermolecular interactions (work of adhesion) among the drug, matrix, and solvent when the incorporated hydrophobic SP moieties transform into the hydrophilic merocyanine form upon light irradiation without degradation and disruption of the DDS. The change in how the copolymer composition (hydrophilicity and content) and the lipophilicity of the drug (log P) affect the release profile was investigated. A thermodynamic model, based on Hansen solubility parameters, was developed to design and optimize the polymer composition of the IPNs to obtain the most efficient light-triggered drug release and suppression of the premature release. The developed IPNs showed excellent result for dopamine, l-dopa, and prednisone with around 90-95% light-triggered release. The model was applied to study the release behavior of drugs with different log P and to estimate if the light-induced hydrophobic-to-hydrophilic switch can overcome the work of adhesion between polymers and drugs and hence the desorption and release of the drugs. To the best of our knowledge, this is the first time that work of adhesion is used for this aim. Comparing the result obtained from the model and experiment shows that the model is useful for evaluating and estimating the release behavior of specific drugs merocyanine, IPN, DDS, and spiropyran.

High-Throughput Synthesis and Screening of Rapidly Degrading Polyanhydride Nanoparticles.

Combinatorial techniques can accelerate the discovery and development of polymeric nanodelivery devices by pairing high-throughput synthesis with rapid materials characterization. Biodegradable polyanhydrides demonstrate tunable release, high cellular internalization, and dose sparing properties when used as nanodelivery devices. This nanoparticle platform shows promising potential for small molecule drug delivery, but the pace of understanding and rational design of these nanomedicines is limited by the low throughput of conventional characterization. This study reports the use of a high-throughput method to synthesize libraries of a newly synthesized, rapidly eroding polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and sebacic acid (SA) monomers. The high-throughput method enabled efficient screening of copolymer microstructure, revealing weak block-type and alternating architectures. The high-throughput method was adapted to synthesize nanoparticle libraries encapsulating hydrophobic model drugs. Drug release from these nanoparticles was rapid, with a majority of the payload released within 3 days. Drug release was dramatically slowed at acidic pH, which could be useful for oral drug delivery. Rhodamine B (RhoB) release kinetics generally followed patterns of polymer erosion kinetics, while Coomassie brilliant blue (CBB) released the fastest from the slowest degrading polymer chemistry and vice versa. These differences in trends between copolymer chemistry and release kinetics were hypothesized to arise from differences in mixing thermodynamics. A high-throughput method was developed to synthesize polymer-drug film libraries and characterize mixing thermodynamics by melting point depression. Rhodamine B had a negative χ for all copolymers with <30 mol % CPTEG tested, indicating a tendency toward miscibility. By contrast, CBB χ increased, eventually becoming positive near 15:85 CPTEG:SA, with increasing CPTEG content. This indicates an increasing tendency toward phase separation in CPTEG-rich copolymers. These in vitro results screening polymer-drug interactions showed good agreement with in silico predictions from Hansen solubility parameter estimation and were able to explain the observed differences in model drug release trends.

Development and evaluation of dapsone tablets coated for specific colon release.

Objective: Drug release systems based on colonic microbiota have been explored with the use of polysaccharides, which are biodegradable. In order to modulate the release into the colon, dapsone tablets were developed, coated with Surelease® and chondroitin sulfate (SC).Methods: The formulation was developed using the wet granulation method, in the form of 9-millimetre circular tablets. The coating was applied in a perforated basin-type coating using different proportions of Surelease® and chondroitin sulfate. The tablets were assessed according to the criteria of mean weight, hardness, and friability. The dissolution test was performed in the dissolver IV apparatus, in media simulating the gastrointestinal system environments (pH 1.2-pH 6.0 and pH 7.2) for 420 min. The results were analyzed by statistical analysis and factorial design.Results: The results of mean weight, hardness, and friability met the pharmacopeial specifications. In the dissolution test, the results obtained demonstrated that Surelease® is able to offer effective protection to the drug, releasing minimum rates when used at 6% or 10% of the tablet's weight gain. The experiments showed that the drug was not able to spread through the coatings manufactured exclusively with Surelease® or even when SC was incorporated in different proportions. Only in the formulation where SC was included in the highest proportion (10%), and the weight gain of the tablet was lower (6%), the release of dapsone increased, reaching 9.5% of drug released. Through factorial planning, it was observed that the drug release rate increases when the weight gain of the tablet remains at the lower level (6%), while the amount of polysaccharide is increased (90:10).Conclusions: The data indicate that the proportion of polysaccharide for ethyl cellulose in the film and the thickness of the coating are the key parameters in controlling the release of the drug from the system.

Latanoprost uptake and release from commercial contact lenses.

This study investigated the potential of delivering an anti-glaucoma drug using commercial silicone hydrogel (SiHy) contact lenses. The moderately hydrophobic drug latanoprost was rapidly loaded in 4 min by swelling contact lenses in a solution of the drug in n-propanol. A fraction of the drug was radiolabeled, thus allowing measurement of the uptake and subsequent release of drug into artificial tear fluid. Three questions were addressed: (1) how much drug can be loaded into each type of lens, (2) how fast is drug release, and (3) how are these values related to the contact lens chemistry. The results showed that much more latanoprost could be loaded into SiHy lenses than a conventional contact lens of poly(hydroxyethyl methacrylate). The drug uptake correlated with the amount of swelling in n-propanol, with Galyfilcon lenses having the greatest swelling and highest drug uptake. The drug release from the SiHy lenses occurred over days, whereas the conventional lens released nearly all drug in a burst over a few hours. To examine correlations between lens chemistry, drug chemistry and uptake, and solvent chemistry, the Hansen solubility parameters were calculated using estimates of contact lens chemistry. These results showed that drug uptake in SiHy lenses correlated with favorable solubility parameter interactions between the n-propanol and the lens material, but did not correlate with interactions between the drug and the lens materials.

Five-Stage Approach for a Systematic Screening and Development of Etravirine Amorphous Solid Dispersions by Hot-Melt Extrusion.

The aim of this study was to develop a fast, effective, and material sparing screening method to design amorphous solid dispersions (ASDs) of etravirine to drive more effectively the development process, leading to improved bioavailability (BA) and stability. A systematic step-by-step approach was followed by combining theoretical calculations with high-throughput screening (HTS) and software-assisted multivariate statistical analysis. The thermodynamic miscibility and interaction of the drug in several polymers were predicted using Hansen solubility parameters (δ). The selected polymers were evaluated by HTS, using solvent evaporation. Binary compositions were evaluated by their solubilization capacity and physical stability over 2 months. JMP 14.0 was used for multivariate statistical analysis using principal components analysis. Extrusion was performed in Thermo Scientific HAAKE MiniLab II, and extrudates were characterized by assay, related substances, dissolution, and physical state (polarized light microscopy (PLM), Raman spectroscopy, and X-ray powder diffraction (XRPD)). A short stability study was performed where milled extrudates were exposed to 25 °C/60%RH and 40 °C/75%RH for 3 months. Through thermodynamic predictions, five main polymers were selected. The HTS enabled the evaluation of 42 formulations for solubilization capacity and physical stability. The three most promising compositions were selected for hot-melt extrusion (HME) tests. In general, a good correlation was found among the results of theoretical predictions, HTS, and HME. Poly(vinylpyrrolidone) (PVP)-based formulations were shown to be easily extrudable, with low degradation and complete amorphicity, whereas in Soluplus, the drug was not miscible, leading to a high crystalline content. The drug release rate was improved more than two times with PVP, and the manufactured ASD was demonstrated to be stable physically and chemically. A fast and effective screening technique to develop stable ASDs for a poorly soluble drug was successfully developed as applied to etravirine. The given method is easy to use, requires a low amount of drug, and is fairly accurate in predicting the amorphization of the drug when formulated. The success of HME formulation development of etravirine was undoubtedly enhanced with this high-throughput tool, which led to the identification of extrudates with improved biopharmaceutical properties. The structural characterization performed by PLM, XRPD, and Raman spectroscopy demonstrated that the HME prototype was essentially amorphous. The unexpected stability at 40 °C/75%RH was correlated with the presence of molecular interaction characterized by Raman spectroscopy.

Formulation development of lipid nanoparticles: Improved lipid screening and development of tacrolimus loaded nanostructured lipid carriers (NLC).

Lipid nanoparticles are well-known nanocarriers for improved drug delivery. Their formulation development typically involves three formulations steps. In the first part a suitable lipid mixture which enables a high loading capacity and high encapsulation efficacy of the active needs to be identified (lipid screening). In the second step suitable stabilizers that enable the production of small-sized lipid nanoparticles with narrow size distribution and sufficient physical stability need to be identified (stabilizer screening, optimization of production parameters) and in the third step the biopharmaceutical efficacy needs to be evaluated. Based on the results obtained the formulations will require further optimization. The classical formulation development of lipid nanoparticles and especially the classical lipid screening is tedious. Therefore, in this study, a novel approach for the lipid screening that was based on the determination of the Hansen solubility parameters was evaluated and the results obtained were compared to the results from the classical model. Tacrolimus was used as a model drug. Results showed that both lipid screenings led to similar results, indicating that the new approach can be used for future developments. The optimized formulation was composed of a lipid matrix system that contained waxes, triglycerides and monoacylglycerols with various carbon chain lengths (C8, C10, C16, C18) and enabled an encapsulation efficiency of ~99%. The stabilizer screening showed that surfactants with high HLB values, lower molecular weight, and shorter alkyl chain length tended to form smaller particles with narrower size distribution and better physical stability. The most suitable surfactant was found to be a caprylyl/capryl glucoside (Plantacare® 810), a PEG-free stabilizer, that is extremely mild for atopic skin. It led to particle sizes of about 200 nm and a zeta potential well above |30| mV. The optimized formulation contained 0.1% tacrolimus and possessed good physical stability. In conclusion, an optimized method for the selection of lipids that results in a limited number of experiments could be established and tacrolimus loaded lipid nanoparticles with similar drug load as a marketed formulation was successfully developed in this study.

Physicochemical stimuli as tuning parameters to modulate the structure and stability of nanostructured lipid carriers and release kinetics of encapsulated antileprosy drugs.

To unveil the effect of electrolyte concentration, pH and polymer addition on Tween 80 stabilized nanostructured lipid carriers (NLCs, based on dialkyldimethylammonium bromides DxDAB and Na oleate), an in-depth scattering analysis was performed. Dynamic and static light scattering (DLS/SLS) and small-angle neutron scattering (SANS) techniques along with zeta potential studies were exploited to understand the structural evolution and physical stability of NLCs. In these experiments, we varied the salt concentration, pH, and the admixture of Pluronic F127 in order to elucidate their effect on NLC morphologies. In most cases, two populations of different sizes are present which differ by one order of magnitude. The antileprosy drugs (ALD) Rifampicin and Dapsone were encapsulated in NLCs and the vector properties were assessed for a series of DxDAB (where x = 12, 14, 16 and 18) NLCs. The influence of composition on the entrapment and release behavior of NLCs was investigated: The size of NLCs correlates with the release rate of the incorporated drug. The interaction of drug-loaded NLCs with bovine serum albumin was studied to understand the release of ALD in the plasma.

Systematic evaluation of the impact of solid-state polymorphism on the bioavailability of thalidomide.

Thalidomide (TLD) is used to treat erythema nodosum leprosum (ENL), multiple myeloma, aphthous ulceration and wasting syndrome in HIV patients. The API can be found in two crystalline habits known as α-TLD and ß-TLD. The saturation solubility (Cs) and the dissolution profiles under non-sink and sink conditions of both polymorphs were assessed. In addition, mini-capsules containing α-TLD or ß-TLD without excipients were orally given (10 mg/kg) to Wistar rats. An intravenous (i.v.) dose was also administrated (5 mg/kg). The Cs values for α-TLD and ß-TLD were not significantly different (α = 56.2 ±â€¯0.5 µg·mL-1; ß = 55.2 ±â€¯0.2 µg·mL-1). However, the dissolution profile of α-TLD presented the fastest rate and the largest extension of drug dissolution than that from ß-TLD (80% in 4 h versus 55% in 4 h). The α-TLD provided a more favorable pharmacokinetic than the ß-TLD (maximum plasma concentration - Cmax: 5.4 ±â€¯0.90 µg·mL-1versus 2.6 ±â€¯0.2 µg·mL-1; area under the curve of the concentration-time profile from time zero to infinity - AUC0-∞: 44.3 ±â€¯8.8 µg·h·mL-1versus 33.9 ±â€¯4.7 µg·h·mL-1; absolute bioavailability - F: 92.2 ±â€¯18.5% versus 70.5 ±â€¯9.9%, respectively). Drug suppliers and pharmaceutical companies should strictly control the technological processes involved in the TLD API synthesis as well as in the production of the pharmaceutical dosage form in order to guarantee the inter-batch homogeneity and therefore, product compliance.

Solid-State Behavior and Solubilization of Flash Nanoprecipitated Clofazimine Particles during the Dispersion and Digestion of Milk-Based Formulations.

Clofazimine, a drug previously used to treat leprosy, has recently been identified as a potential new drug for the treatment for cryptosporidiosis: a diarrheal disease that contributes to 500 000 infant deaths a year in developing countries. Rapid dissolution and local availability of the drug in the small intestine is considered key to the treatment of the infection. However, the commercially available clofazimine formulation (Lamprene) is not well-suited to pediatric use, and therefore reformulation of clofazimine is desirable. Development of clofazimine nanoparticles through the process of flash nanoprecipitation (FNP) has been previously shown to provide fast and improved drug dissolution rates compared to clofazimine crystals and Lamprene. In this study, we investigate the effects of milk-based formulations (as possible pediatric-friendly vehicles) on the in vitro solubilization of clofazimine formulated as either lecithin- or zein/casein-stabilized nanoparticles. Milk and infant formula were used as the lipid vehicles, and time-resolved synchrotron X-ray scattering was used to monitor the presence of crystalline clofazimine in suspension during in vitro lipolysis under intestinal conditions. The study confirmed faster dissolution of clofazimine from all the FNP formulations after the digestion of infant formula was initiated, and a reduced quantity of fat was required to achieve similar levels of drug solubilization compared to the reference drug material and the commercial formulation. These attributes highlight not only the potential benefits of the FNP approach to prepare drug particles but also the fact that enhanced dissolution rates can be complemented by considering the amount of co-administered fat in lipid-based formulations to drive the solubilization of poorly soluble drugs.

pH-responsive chitosan based hydrogels affect the release of dapsone: Design, set-up, and physicochemical characterization.

Dapsone (DAP) is a bactericidal agent used in the treatment of leprosy, caused by Mycobacterium leprae. Despite its therapeutic potential, DAP has low solubility, which results in allow therapeutic index and a high microbial resistance. Recently, new approaches were used to increase the DAP solubility. In particular, the use of interpenetrating polymer network (IPN)-hydrogels based chitosan (CS) for the controlled release of DAP provides some advantages because they can modify their swelling properties and network structures as a response to environmental stimuli. The aim of this study was to synthesize and physicochemically characterize pH-responsive chitosan/polymer hydrogels to control the release of DAP. For this reason, different combination of polymers, such as polyvinyl pyrrolidone, polyethylene glycol and hydroxypropyl methylcellulose, and concentrations of the cross-linking agents (glutaraldehyde) were used and then blended to the CS. The resulting hydrogels were evaluated in terms of physicochemical and swelling properties, rheological analysis and in vitro release of DAP at different pHs (1.2-6.8). Hydrogels were further characterized by Fourier transformed infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) analysis. pH-responsive DAP-loaded hydrogels may represent the set-up for developing potential oral formulations for the treatment of leprosy caused by Mycobacterium leprae.

Systematic modifications of amino acid-based organogelators for the investigation of structure-property correlations in drug delivery system.

Thermogels, used as multi-functional drug-loading materials, have properties that mainly rely on their gelator structure. Although a large variety of organogel systems are used as drug delivery carriers, relatively few have been investigated in terms of their structure-property correlations based on amino acid derivative gelators. Here, a series of amino acid based gelators were synthesized to explore the role of the gelator structure on functional properties, with the aim of establishing a connection between the molecular parameters and gel properties. By varying the three substitutions of the gelator backbone, it was found that a comprehensive interaction, consisting of hydrophobic forces, H-bonding interactions, conformational flexibility and steric repulsion, play a crucial role in determining the gelation properties. Hansen solubility parameters were employed to explore the solvent effect on the network forming and gel properties. From an analysis of the morphologies obtained from polarized optical microscope (POM), atomic force microscopic images (AFM) and scanning electron microscopy (SEM), the gelator structure was found to have an impact on the self-assembly. According to the X-ray diffraction (XRD), the possible conformations adopted by the gelators were revealed through molecular modelling. The ability to form intermolecular H-bonding is vital in molecular packing and, thus, gelation. A structure-property relationship was developed and proposed to provide a theoretical basis for controllable drug delivery implants.

Alginate as a potential diphase solid dispersion carrier with enhanced drug dissolution and improved storage stability.

The objective of this study was to explore the feasibility of using alginate as a promising diphase solid dispersion carrier to enhance dissolution rate of BCS II drugs with improved stability. Taking lovastatin and indomethacin as model drugs, solvent evaporation method was used to prepare solid dispersions. The drug/polymer compatibility was predicted by Hansen solubility parameter and the drug/polymer ratio was screened based on dissolution study, drug existing state in solid dispersion was characterized by DSC and XRPD. Accelerated stability of the solid dispersion was assessed and compared with that of HPMCAS based system. Phase behavior of the solid dispersion before and after stability study was characterized using polar microscope and Raman mapping. It was found that the optimal drug/alginate ratio was drug dependent and drug existing state was related to drug/alginate miscibility. Stability studies revealed that alginate improved the stability of solid dispersions regardless of drug existing state and a better stability was obtained compared to HPMCAS based system. Raman mapping and SEM study revealed that micro phase separation of solid dispersion was the main reason for the slight decrease in drug dissolution after accelerating experiment. In conclusion, alginate can be used as a promising diphase solid dispersion carrier with significantly improved dissolution rate and storage stability.

pH-sensitive nanoparticles for improved oral delivery of dapsone: risk assessment, design, optimization and characterization.

AIM: To optimize the production of pH-sensitive dapsone (DAP) nanoparticles based on Eugradit L100 (NPs-EL100-DAP) for oral delivery. MATERIALS & METHODS: NPs-EL100-DAP were optimized using a Plackett-Burman design and a Box-Behnken design. The physicochemical properties of the obtained nanoparticles were monitored by microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release assays, and examined for cytotoxicity and permeation across intestinal barrier. RESULTS: The in vitro release assay of NPs-EL100-DAP confirmed the nanoparticles' pH sensitivity and the ability to deliver DAP at intestinal environment. NPs-EL100-DAP demonstrated enhanced intestinal interactions in comparison to free DAP, across Caco-2 monolayers. CONCLUSION: These studies demonstrate the potential of NPs-EL100-DAP as a therapeutic platform for oral treatment of leprosy.

Modified bacterial cellulose scaffolds for localized doxorubicin release in human colorectal HT-29 cells.

Bacterial cellulose (BC) films modified by the in situ method with the addition of alginate (Alg) during the microbial cultivation of Gluconacetobacter hansenii under static conditions increased the loading of doxorubicin by at least three times. Biophysical analysis of BC-Alg films by scanning electron microscopy, thermogravimetry, X-ray diffraction and FTIR showed a highly homogeneous interpenetrated network scaffold without changes in the BC crystalline structure but with an increased amorphous phase. The main molecular interactions determined by FTIR between both biopolymers clearly suggest high compatibility. These results indicate that alginate plays a key role in the biophysical properties of the hybrid BC matrix. BC-Alg scaffold analysis by nitrogen adsorption isotherms revealed by the Brunauer-Emmett-Teller (BET) method an increase in surface area of about 84% and in pore volume of more than 200%. The Barrett-Joyner-Halenda (BJH) model also showed an increase of about 25% in the pore size compared to the BC film. Loading BC-Alg scaffolds with different amounts of doxorubicin decreased the cell viability of HT-29 human colorectal adenocarcinoma cell line compared to the free Dox from around 95-53% after 24h and from 63% to 37% after 48 h. Dox kinetic release from the BC-Alg nanocomposite displayed hyperbolic curves related to the different amounts of drug payload and was stable for at least 14 days. The results of the BC-Alg nanocomposites show a promissory potential for anticancer therapies of solid tumors.

Simple measurements for prediction of drug release from polymer matrices - Solubility parameters and intrinsic viscosity.

PURPOSE: This study describes how protein release from polymer matrices correlate with simple measurements on the intrinsic viscosity of the polymer solutions used for casting the matrices and calculations of the solubility parameters of polymers and solvents used. METHOD: Matrices of poly(dl-lactide-co-glycolide) (PLGA) were cast with bovine serum albumin (BSA) as a model drug using different solvents (acetone, dichloromethane, ethanol and water). The amount of released protein from the different matrices was correlated with the Hildebrand and Hansen solubility parameters of the solvents, and the intrinsic viscosity of the polymer solutions. Matrix microstructure was investigated by transmission and scanning electron microscopy (TEM and SEM). Polycaprolactone (PCL) matrices were used in a similar way to support the results for PLGA matrices. RESULTS: The maximum amount of BSA released and the release profile from PLGA matrices varied depending on the solvent used for casting. The maximum amount of released BSA decreased with higher intrinsic viscosity, and increased with solubility parameter difference between the solvent and polymer used. The solvent used also had an effect on the matrix microstructure as determined by TEM and SEM. Similar results were obtained for the PCL polymer systems. CONCLUSIONS: The smaller the difference in the solubility parameter between the polymer and the solvent used for casting a polymer matrix, the lower will be the maximum protein release. This is because of the presence of smaller pore sizes in the cast matrix if a solvent with a solubility parameter close to the one of the polymer is used. Likewise, the intrinsic viscosity of the polymer solution increases as solubility parameter differences decrease, thus, simple measurements of intrinsic viscosity and solubility parameter difference, allow the prediction of protein release profiles.