Preparation and Characterization of Solid Dispersions of Silymarin with Polyethylene Glycol 6000

Aim To prepare and characterize solid dispersions of silymarin with the intention of improving their dissolution properties. Methods The solid dispersions were prepared by the fusion method with polyethylene glycol 6000(PEG 6000) as the carrier. Evaluation of the properties of the dispersions was performed using dissolution studies, X ray powder diffraction and Fourier transform infrared (FT IR) spectroscopy. Results The rate of dissolution of silymarin was considerably improved as compared with pure silymarin when formulated in solid dispersions with PEG 6000. The data of the X ray diffraction showed some changes in the parameters of lattice spacing [ d ], peak position and relative intensities. FT IR together with those from X ray diffraction showed the absence of well defined drug polymer interactions. Conclusion The dissolution improvement of poorly soluble silymarin could be illuminated by the changes of the lattice parameters of PEG 6000 and the drug.

Preparation,physicochemical characterization and cyctotoxicity of solid dispersion of paclitaxel and polyvinylpyrrolidone

The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid dispersion systems were prepared by solvent method. The release rate ofpaclitaxel was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The cytotoxicities ofpaclitaxel in solid dispersion to the SKOV-3 cells were assayed by a SRB staining method. The results showed that the solubility and dissolution rate of paclitaxel were significantly improved in solid dispersion system compared with that of the pure drug and physical mixture. The results of DSC and PXRD showed that the paclitaxel in solid dispersion was amorphous form. No paclitaxel crystals in the solid dispersions was found during SEM analysis. Cytotoxicity study suggested that the inhibitory rates of PTX-PVP solid dispersion to SKOV-3 cells were higher than that of pure paclitaxel. The solubility and dissolution of paclitaxel were improved by solid dispersion technique. In vitro cytotoxicity of paclitaxel in solid dispersion was higher than that of pure drug.

Dissolution Improvement of Cisapride by Solid Dispersion with HPMC

To prepare a solid dispersion of cisapride with hydroxypropylmethyl cellulose(HPMC E5 LV) as carrier for the purpose of accelerating the in vitro drug release by means ofimproving the solubility of the model drug. Methods Alcohol and simulated gastric fluid (SGF) wereused to dissolve cisapride and HPMC in order to make the model drug dispersed homogeneously in thecarrier. The HPMC-cisapride solid dispersion was then obtained by conventional solvent evaporationmethod. Powder X-ray diffraction (XRD) was used to measure the diffraction peaks of pure carrier,pure cisapride, physical mixture of HPMC with cisapride (4:1), and HPMC-cisapride solid dispersion(4:1) to confirm the crystal existence. The solubility of pure drug and HPMC-cisapride soliddispersion was measured with water, SGF and simulated intestinal fluid (SIF) . The in vitro drugreleases of the sustained release tablet prepared with pure cisapride or HPMC-cisapride soliddispersion were investigated with water and SGF as media, respectively. Results No diffraction peakswere found by X-ray diffraction in the HPMC-cisapride solid dispersion (4:1), indicating that thedrug existed in an amorphous form at that drug-carrier ratio. Compared with the pure drug, thesolubilities of HPMC-cisapride solid dispersion are increased by 239.4% in SGF, 132.6% in water, and117.9% in SIF. According to the in vitro drug release, the sustained release tablet prepared withHPMC-cisapride solid dispersion had a faster drug release than did that prepared with pure drug. Thein vitro drug release profiles were found to comply with Higuchi's rule. Conclusion The in vitrodrug release of the sustained release tablet made by HPMC-cisapride solid dispersion is improvedowing to the increased drug solubility.

Preparation and physicochemical characterization of solid dispersion of quercetin and polyvinylpyrrolidone

Aim The objective of this study was to prepare and characterize quercetin-polyvinylpyrrolidone （Qurc-PVP） solid dispersion with the intention of improving its dissolution properties, Methods Qurc-PVP sclid dispersion was prepared by solvent method. The release rate of quercetin was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, infrared spectroscopy （IR）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. Results The results showed that the dissolution rate of quercetin was significantly improved by solid dispersion compared to that of the pure drug and physical mixture, Solubility studies revealed a markedly increase in the solubility of quercetin. The results of DSC and PXRD showed that the quercetin in solid dispersion was amorphous form. From SEM analysis, there was no quercetin crystal observed in the solid dispersions. Conclusion The solubility and dissolution of quercetin were improved by solid dispersion technique.

A RP-HPLC method for determination of paclitaxel in its solid dispersion

Aim To develop and validate a RP-HPLC method for the analysis of paclitaxel in a solid dispersion. Methods Paclitaxel and the internal standard norethisterone were separated using a Phenomenex ODS 3 column and monitored at a wavelength at 227 nm. The isocratic mobile phase consisting of methanol-acetonitrile-water （40：30：30, V/V） was pumped at a flow-rate of 1.0 mL·min^-1. The dissolution studies were performed according to published studies. Results Under these chromatographic conditions, the calibration curve was linear in the range of 4-40 μg·mL ^-1 with the correlation coefficient of 0.9999. The mean recovery was 98.42 % （RSD = 1.19 %）. At the 60 min time point, the dissolution of paclitaxel from the solid dispersion was nearly 100 %, however, the original form of paclitaxel was about 30 %. Conclusion The method was proven to be specific, accurate and precise for determining the dissolution of paclitaxel from solid dispersion.

Improved dissolution and bioavailability of silymarin delivered by a solid dispersion prepared using supercritical fluids

The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitro and in vivo,compared with pure SM powder.The particle sizes,stability,and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation(SE)were investigated.Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS,and the hydrophilic polymer,polyvinyl pyrrolidone K17,was selected with a ratio of 1:5 between SM and the polymer.Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state.The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent(ethanol)was detected using gas chromatography.In vitro drug release was increased from the SM-SDSEDS,as compared with pure SM powder or SM-SD-SE.In vivo,the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher,respectively,after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension.These results illustrated the potential of using SEDS to prepare SM-SD,further improving the biopharmaceutical properties of this compound.

Development and evaluation of lafutidine solid dispersion via hot melt extrusion:Investigating drug-polymer miscibility with advanced characterisation

In current study,immediate release solid dispersion(SD)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)technique.Amphiphilic Soluplus
used as a primary solubilizing agent,with different concentrations of selected surfactants like PEG 400,Lutrol F127(LF127),Lutrol F68(LF68)were used to investigate their influence on formulations processing via HME.Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable.On the contrary,traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry(DSC),X-ray diffraction(XRD),scanning electron microscopy(SEM)and Raman spectroscopy.Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC.Atomic Force microscopy(AFM)studies revealed drugpolymer molecular miscibility and surface interaction at micro level.1HeCOSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus
,with chemical shift drifting and line broadening.MD simulation studies using computational modelling showed intermolecular interaction between molecules.Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems.Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD.The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.

Advances in the development of amorphous solid dispersions:The role of polymeric carriers

Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations.Polymer selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the ASD.This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation methods.Furthermore,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.

The characterization and dissolution performances of spray dried solid dispersion of ketoprofen in hydrophilic carriers

Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API.However,there are inconsistent dissolution performances of solid dispersion reported which entails further investigation.In this study,solid dispersions of ketoprofen in three hydrophilic carriers,i.e.PVP K30,PVPVA 6:4 and PVA were prepared and characterized.Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API.This result is coinciding to evaluation of drug-polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug-polymer interaction.XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA.Interestingly,dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system.Thus,it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.

Dissolution improvement by solid dispersions composed of nifedipine, Eudragit?E and silica from rice husk

Nifedipine is a practically water-insoluble drug used therapeutically as a calcium-channel blocker for systemic and coronary vasodilation.Poorly soluble drugs that undergo dissolution rate-limited gastrointestinal absorption generally show increased bioavailability when dissolution is improved by formulation techniques[1].In solid dispersion system,a drug may exist as an amorphous form in polymeric carriers,and this may result in improved solubility and dissolution rate as compared with crystalline drug.Solid dispersion can be prepared by either fusion or solvent method[2].

Solid dispersion in the development of a nimodipine delayed-release tablet formulation

Nimodipine(NMD)is a dihydropyridine calcium channel blocker with selectivity for cerebral blood vessels and the major therapeutic indication of NMD is for the prevention and treatment of delayed ischemic neurological disorders and other cerebrovascular disorders,such as stroke which is associated with biological rhythm.This study was mainly designed to solve the drawback of conventional NMD solid dosage form,low bioavailability and limited clinical efficacy,by preparing enteric solid dispersion(SD)and the SD was prepared via melting method.The physical state of the dispersed NMD in the polymer matrix was characterized by differential scanning calorimetry(DSC),powder X-ray diffraction(PXRD)and dissolution studies.Compared with pure drug and physical mixture,the dissolution of NMD-SD was enhanced dramatically(about 80%).Furthermore,in consideration of the biological rhythm of stroke,we first obtained a delayed-release tablet containing NMD-SD by a direct powder compression method.As shown in the dissolution studies,the tablet released less than 10%in the artificial gastric acid in the initial 2 h and released 32.1%,75%,more than 90%at 4,10 and 14 h respectively in the artificial intestinal fluid.This investigation has solved the problems of oral solid dosage forms of NMD,and it has the good industry prospect.

Interaction of Puerarin with Phospholipid in Solid Dispersion

Aim To study the interaction of puerarin (PU) with phospholipid (PL) in soliddispersion. Methods PU/PL solid dispersion was prepared with solvent evaporation and theinteraction between PU and PL was studied by analysis of their ultraviolet spectra, infraredspectra, ~1H NMR spectra and thin layer chromatogram. Results In chloroform the maximum absorptionpeak of PU in PU/PL mixture was located at 243 nm, but 251 nm for that of PU in solid dispersion.However in methanol, QU in mixture or solid dispersion had the same maximum absorption peak locationin ultraviolet spectra. Compared with the infrared spectra of mixture, that of solid dispersionshowed the specific absorption peak location of benzene ring framework in PU molecule was markedlychanged, the stretching vibration peak of P= O in PL molecule was shifted to high wavenumbers andthe stretching vibration peak of C = C in PL molecule was disappeared. In ~1H NMR spectra, most ofthe signals from PU in solid dispersion were weaken markedly or disappeared and the signals from thepolar part of PL molecule were significantly changed. PU and PL in solid dispersion could beseparated on silica gel plate with the mixed solvent of chloroform, methanol and water (65:25:5) orethyl acetate and methanol (10:1) . Conclusion In solid dispersion the benzene ring framework of PUmolecule could act with the polar part and unsaturated part of PL molecule through charges transfer,and the interacted part could be surrounded by fat chains of PL molecule.

Development,characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug

The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists.Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively simple method for increasing dissolution rates.The objective of this study was to improve solubility,release and comparability of dissolution of a poorly soluble drug using two different types of formulations(solid dispersions and microspheres).Hydrochlorothiazide was used as a model drug.The solid dispersions and microspheres were prepared by solvent evaporation method using ethyl cellulose,hydroxypropyl methylcellulose in different drug-to-carrier ratios(1:1,1:2 w:w).The prepared formulations were evaluated for interaction study by Fourier transform infrared spectroscopy,differential scanning calorimetry,percentage of practical yield,drug loading,surface morphology by scanning electron microscopy,optical microscopy and in-vitro release studies.The results showed no interaction between the drug and polymer,amorphous state of solid dispersions and microspheres,percentage yield of 42.53%to 78.10%,drug content of 99.60%to 99.64%,good spherical appearance in formulation VI and significant increase in the dissolution rate.

Transdermal Study of Curcumin Solid Dispersion Microneedles in vitro

[Objectives]To investigate the in vitro transdermal effect of curcumin solid dispersion needles prepared with povidone K 30(PVP K30),polyethylene glycol 6000(PEG 6000)and poloxamer 188(block polyether F68,poloxamer 188,F68)as carrier matrix,respectively.[Methods]Vertical Franz diffusion cell and HPLC method were used to detect the cumulative penetration and skin retention of the microneedles within 12 h.[Results]Within 12 h,the cumulative penetration of PVP K30 microneedles was as high as 7.098μg/cm2,and the skin retention reached 35.28μg/cm2;PEG 6000 and poloxamer 188 microneedles all showed good transdermal effect;while normal curcumin solid dispersion(control)had no obvious transdermal effect.[Conclusions]The transdermal penetration of curcumin is improved after prepared into solid dispersion microneedles,and among different matrixes,PVP K30 is the best choice.

Development and Evaluation of Stable Paracetamol Loaded Solid Dispersion with Enhanced Analgesic and Hepatoprotective Property

Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.

Formulation,in-vitro Evaluation and Dissolution Enhancement of Griseofulvin by Solid Dispersion Method

Introduction:Griseofulvin is an antifungal drug belonging to Biopharmaceutical Classification System(BCS class II)having low solubility.Objectives:To formulate,evaluate and enhance the dissolution of poorly water soluble drug Griseofulvin by using solid dispersion method.Methods:Six formulations were prepared by solid dispersion method using Polyethylene Glycol(PEG 6000)125 mg,0 mg,62.5 mg,100 mg,25 mg,150 mg and superdisintegrants Crospovidone 0 mg,125 mg,62.5 mg,100 mg,25 mg,150 mg in all batches respectively.Findings:Satisfactory results were obtained from evaluation of physical characteristics of Griseofulvin tablets including:carr’s compressibility index(17.5±0.19%to 11.76±0.67%),Hausner ratio(1.21±0.01 to 1.13±0.02)and post compression parameters including:thickness(5.16±0.02 mm to 4.57±0.19 mm),friability(0.024%to 0.322%),hardness(4±0.28 kg/cm^(2)to 5±0.57 kg/cm^(2)),disintegration time(14-870 seconds).Conclusions:F3 was best formulation among all formulated batches with in-vitro drug release 30.05%in 10 minutes,69.21%in 30 minutes and 97.11%in 45 minutes.This indicated that formulation F3 batch with PEG 6000 of 62.5 mg and crospovidone 62.5 mg showed increased dissolution.

Physicochemical Characterization and Solubility Enhancement Studies of Mebendazole Solid Dispersions in Solvent Mixtures

Abstract： The objective was to obtain solid dispersion to improve the dissolution rate, solubility and oral absorption of MB （mebendazole）, poor water-soluble drugs. The new formulation was characterized by DSC （differential scanning calorimetry）, PXRD （powder X-ray diffraction）, FT-1R （fourier transform infrared spectroscopy） and STEM （scanning transmission electron microscopy） methods. Solid dispersions of MB with polyvinylpyrrolidone K-30 （PVP K30） were prepared by solvent evaporation method. The solubility of MB （original powder） and that of the solid dispersions was measured at 25℃ in ethanol-water. The aqueous solubility of MB was favoured by the presence of the polymer in solvent mixtures. Combination of solid dispersions with co-solvents increased the water solubility of MB in a larger extent that each method separately. Solubility parameter （o） was used to relate to solubility profiles. MB and the solid dispersions show a solubility curve with a single peak at 51 = 30.78 MPav2. Solid state characterizations indicated that the solid dispersion exist an amorphous material entrapped in polymer matrix getting highest improvement in wettability and solubility.

Mapping multiple phases in curcumin binary solid dispersions by fluorescence contrasting

The microphases and miscibility in binary curcumin(Cur)solid dispersions(SDs)with amorphous polyvinylpyrrolidone K30(PVP K30)and semi-crystalline poloxamer(P407)and poly(ethylene glycol)6000(PEG6000)as carriers were investigated by fluorescence contrasting utilizing confocal laser scanning microscopy.A super sensitive fluorophore P4 with typical aggregation-caused quenching properties was employed to stain the continuous polymer phases and contrasted with the autofluorescence of the model drug Cur.In addition,differential scanning calorimetry(DSC)and powder X-ray diffraction(PXRD)were utilized to assist in explanation of the fluorescence results.In all three SD systems,there is always a homogenous polymer phase stained by P4 and it is difficult to adulterate Cur crystals by P4.Cur-enriched rather than polymer-enriched domains could be detected.In the Cur-PVP K30 system,Cur exists in an amorphous form at a Cur loading level of 50%and below,while Cur crystallines phase out and continuously grow with the increase of Cur loading from 60%to 90%.The phase behaviors in the Cur-P407 and Cur-PEG 6000 systems are similar but with minor differences.In both systems,Cur phases out as clusters of drug-enriched domains at a loading level of 20%and below,which however cannot be correlated with crystallization,as evidenced by both DSC and PXRD.There is a transition from an amorphous to a crystalline state from 20%to 30%Cur loading,above which Cur crystallines can be detected.It is interesting that a co-mix phase of both Cur-and PEG 6000-enriched domains can be identified at Cur loading levels of 10%and less.Taking together,it is concluded that contrasting Cur autofluorescence with the signals of P4 proves to be a functional strategy to reveal multiple phases in the binary SD systems investigated.

Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in vivo.METHODS:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers.Thermogravimetric analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AESD.Optimal prescriptions were screened via the dissolution degree determination method.Using Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion.Acute toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for toxicity.RESULTS:AE-SD showed that AE existed in the carrier in an amorphous state.Compared with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion.Therefore,it was more suitable as a carrier material for AE-SD.The addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of PVP.The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also optimal.Based on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than AE.The results showed that the drug metabolism in AE-SD was better,and the residence time was shorter.The toxicology study showed that both AE and AE-SD had no toxicity.CONCLUSION:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,as demonstrated by in vitro dissolution experiments.In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo,providing a new concept for the research and development of AE preparations.

An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads:Experimental studies and molecular dynamics analysis

Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.