Polymeric Excipients Research Articles

Bottlebrush Polymer Excipients Enhance Drug Solubility: Influence of End-Group Hydrophilicity and Thermoresponsiveness.

Bottlebrush polymers have great potential as vehicles to noncovalently sequester, stabilize, and deliver hydrophobic small molecule actives. To this end, we synthesized a poly(N-isopropylacrylamide-stat-N,N-dimethylacrylamide) bottlebrush copolymer using ring-opening metathesis polymerization and developed a facile method to control the thermoresponsive properties using postpolymerization modification. Six increasingly hydrophilic end-groups were installed, yielding cloud point temperature control over a range of 22-42 °C. Solubility enhancement of the antiseizure medication, phenytoin, increased significantly with the hydrophilicity of the end-group moiety. Notably, carboxylated bottlebrush copolymers solubilized formulations with higher drug loadings than linear copolymers because they exist as unimolecular nanoparticles with a synthetically defined density of polymer chains that are more stable in solution. This work provides the first investigation of bottlebrush polymers for hydrophobic noncovalent sequestration and solubilization of pharmaceuticals.

Automated PET-RAFT Polymerization Towards Pharmaceutical Amorphous Solid Dispersion Development.

In pharmaceutical oral drug delivery development, about 90% of drugs in the pipeline have poor aqueous solubility leading to severe challenges with oral bioavailability and translation to effective and safe drug products. Amorphous solid dispersions (ASDs) have been utilized to enhance the oral bioavailability of poorly soluble active pharmaceutical ingredients (APIs). However, a limited selection of regulatory-approved polymer excipients exists for the development and further understanding of tailor-made ASDs. Thus, a significant need exists to better understand how polymers can be designed to interact with specific API moieties. Here, we demonstrate how an automated combinatorial library approach can be applied to the synthesis and screening of polymer excipients for the model drug probucol. We synthesized a library of 25 random heteropolymers containing one hydrophilic monomer (2-hydroxypropyl acrylate (HPA)) and four hydrophobic monomers at varied incorporation. The performance of ASDs made by a rapid film casting method was evaluated by dissolution using ultra-performance liquid chromatography (UPLC) sampling at various time points. This combinatorial library and rapid screening strategy enabled us to identify a relationship between polymer hydrophobicity, monomer hydrophobic side group geometry, and API dissolution performance. Remarkably, the most effective synthesized polymers displayed slower drug release kinetics compared to industry standard polymer excipients, showing the ability to modulate the drug release profile. Future coupling of high throughput polymer synthesis, high throughput screening (HTS), and quantitative modeling would enable specification of designer polymer excipients for specific API functionalities.

A new polymer-excipient for ethanol-resistant, sustained-release oral dosage forms.

The use of alcoholic beverages can cause uncontrolled release of drugs from sustained-release solid oral dosage forms and pose severe risks to patient health. The aim of this work was to design a new polymeric excipient with ethanol resistance inherent to the polymer. Polymers were systematically designed, manufactured via emulsion polymerization, and fully characterized. Glass transition temperatures between 10 and 18°C and minimum film forming temperatures between 10 and 25°C were chosen because these parameters are ideal for aqueous film-coating processing. Three model drug formulations were made with the new polymer excipients and tested in the presence and absence of ethanol. The concept of an alcohol resistance factor based on Weibull regression analysis was introduced. In vitro results confirmed the hypothesized structure-function relationship between comonomer composition and ethanol resistance. That is, nonionic hydrophilic functional groups interacted more strongly with the ethanolic solvent, as compared with cationic hydrophilic comonomer that interacted more strongly with the surrounding water molecules. The alcohol resistance factor varied between -44 ± 2% (slower drug release in presence of ethanol) and + 34 ± 0% (faster drug release in presence of ethanol) depending on the comonomer ratio. The main advantages of these new excipients compared with ethanol-resistant excipient blends include ease of use, plasticizers are not necessary, and shorter coating times.

Suppression of the coffee-ring effect by tailoring the viscosity of pharmaceutical sessile drops

The coffee ring effect (CRE) lies at the heart of droplet-based processing techniques where the drying process of the solute-laden droplet leads to the undesirable formation of a ring-like pattern with uneven distribution of the solidified solute. Although the CRE has been well studied, the practical strategies reported in the literature to prevent CRE are still limited. In this study, we aimed to develop a simple practical solution to minimise CRE by adding polymeric excipients to pharmaceutical solutions containing active pharmaceutical ingredients. We investigated the influence of viscosity on multicomponent sessile droplets containing a polymer (chitosan) and a model drug (paracetamol). When dried on glass, a sessile droplet of an aqueous paracetamol solution was shown to recrystallise into an undesired coffee-ring pattern of drug crystals, due to CRE. This peripheral deposition of crystalline solute was suppressed when the formulation was thickened with chitosan. Increasing the viscosity of the solution prevented the CRE by immobilising solute within the droplet, preventing the radial flow of the solute to the edge of the droplet. This study enriches the mechanistic understanding of a simple practical solution to the suppression of CRE which can have wide applications in many industrial sectors including pharmaceutical.

Design of Catalase Monolithic Tablets for Intestinal Targeted Delivery.

Several studies confirmed a correlation between elevated hydrogen peroxide (H2O2) levels in patients with intestinal bowel diseases (IBD) and the negative effects caused by its presence. The objective of this study was to explore the potential use of catalase (CAT) to diminish the level of H2O2 and its deleterious action on intestinal mucosa. Oral dosage forms of a CAT bioactive agent targeted to the intestines were designed and tested in various simulated gastric and intestinal media. Monolithic tablets (30% loading) were prepared using commercial CarboxyMethylCellulose (CMC) or synthesized CarboxyMethylStarch (CMS) and TriMethylAmineCarboxyMethylStarch (TMACMS) as matrix-forming excipients. For starch derivatives, the presence of the ionic groups (carboxymethyl and trimethylamine) was validated by spectral analysis. In vitro studies have shown that tablets formulated with TMACMS and 30% CAT resisted the acidity of the simulated gastric fluid and gradually released the enzyme into the simulated intestinal fluid. The investigation of the CAT release mechanism revealed the role of anionic and cationic groups of polymeric excipients and their involvement in the modulation of the CAT dissolution profile. The proposed drug delivery system can be considered an efficient solution to target CAT release in the intestine and contribute to the reduction of H2O2 associated with intestinal inflammation.

Effect of polymeric excipients on nucleation and crystal growth kinetics of amorphous fluconazole.

Amorphous solids have been widely used to improve the solubility and oral bioavailability of poorly water-soluble drugs. Biocompatible polymeric materials are usually incorporated into formulations to inhibit the crystallization of high-energy amorphous drugs. Crystallization typically consists of two steps, nucleation and crystal growth. The impacts of polymeric excipients on the crystal growth of amorphous drugs have been intensively studied. However, the nucleation behaviors of amorphous drugs in the presence of polymers remain largely unexplored. Herein, we report that three chemically distinct polymers show significantly different effects on nucleation kinetics of amorphous fluconazole (FCZ), a classical antifungal drug. The addition of 10% w/w HPMCAS shows the largest inhibitory effect on the nucleation rates of FCZ, while the same amount of PVP has only a minor effect. Conversely, the nucleation rates for both polymorphs of FCZ are significantly increased in the presence of PEO. In addition, the polymeric additives are found to influence the kinetics of nucleation and crystal growth to a similar extent, suggesting that the two processes may share a similar kinetic barrier. The present study is helpful in the optimization of formulations of amorphous solid dispersions and understanding the nucleation behavior of polymorphic drugs.

Development of a Pediatric Mini-Tablet Formulation for Expedited Preclinical Studies.

Multiple considerations are essential to address the main challenges of dose flexibility and patient adherence in pediatric drug development, particularly for oncology. Mini-tablets, 2mm in diameter, were manufactured using a rotary tablet press at a set weight and compression force level. The physical characteristics were consistent for mini-tablets throughout multiple batches. Polymeric amorphous solid dispersion (ASD) was used as a solubility enhancing technique to increase solubility and exposure of lapatinib. The effects of the polymeric excipient and disintegrant on drug release properties were investigated. While having a lower apparent solubility and shorter storage stability, hydroxypropyl methylcellulose E3 (HPMCE3) formulation provided a higher percentage of drug release compared to hydroxypropyl methylcellulose phthalate (HPMCP). The intermolecular interaction within the ASD system plays a role in the level of apparent solubility, physical stability, and concentration of free drug available in an aqueous environment. Juvenile porcine models at two different weight groups (10 and 20kg) were used to obtain the pharmacokinetic parameters of lapatinib. While the dose-normalized exposure of drug was found to be lower in the pig study, the dose flexibility of mini-tablets enabled a constant dose level to be administered to achieve equivalent plasma concentration-time profiles between the two groups. This linear scaling in the amount of drug in pediatric and adult population has also been observed in human clinical studies.

Sacubitril-valsartan cocrystal revisited: role of polymer excipients in the formulation

ABSTRACT Objectives: This study investigated the impact of polymer excipients on a typical cocrystal for sacubitril (SAC) and valsartan (VAL), aiming to guide optional formulation design and maximize oral bioavailability. Methods: Poly vinyl pyrrolidone (PVP) and hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) were selected. The dissolution/permeation system was used to predict both the kinetics of drug supersaturation and the simple permeation. The intermolecular interaction was analyzed by 1H NMR spectroscopy and molecular dynamics simulation. Pharmacokinetic study was performed to assess the impact of polymer excipients in vivo. Results: Our study found that unappreciated excipients in the formulation, especially some polymers, might compete with the intermolecular hydrogen bonding among the cocrystals components and provide unexpected affinity, and thus leverage the therapeutic benefits. HPMC as a coating excipient used in the Entresto® tablet hampered the supersaturation of API, which led to the poor oral absorption of cocrystals. Conversely, PVP appeared to promote and maintain drug supersaturation, resulting in improved bioavailability of API. Conclusion: In conclusion, understanding the interplay between the cocrystal components and polymers is the key to optimizing the excipients to maximize the performance of cocrystal based oral drug formulation.

Combining crystalline and polymeric excipients in API solid dispersions – Opportunity or risk?

Amorphous solid dispersions (ASDs) are often metastable against crystallization of the active pharmaceutical ingredient (API) and thus might undergo unwanted changes during storage. The crystallization tendency of ASDs is influenced by the API crystallization driving force (CDF) and the mobility of the molecules in the ASD. Low molecular weight-excipients are known to stabilize amorphous APIs in so-called co-amorphous formulations. Due to their success in stabilizing co-amorphous APIs, low-molecular weight excipients might also enhance the stability of polymeric ASDs. In this work, we investigated the potential of combined low-molecular weight excipient/polymer formulations with in-silico tools and validated the predictions with long-term stability tests of the most promising excipient/polymer combinations. The considered critical quality attributes for the ASDs were the occurrence of amorphous phase separation, API CDF, and molecular mobility in the ASD.As an example, carbamazepine/polyvinylpyrrolidone ASDs were investigated combined with the excipients fructose, lactose, sucrose, trehalose, saccharin, tryptophan, and urea. Although all excipients had a negative impact on the ASD stability, saccharin still turned out to be the most promising one. Long-term stability studies with ASDs containing either saccharin or tryptophan verified -in agreement to the predictions- that API crystallization occurred faster than in the reference ASDs without additional excipient.This work showed that the addition of crystalline excipients to polymeric ASDs might not only offer opportunities but might also bear risks for the long-term stability of the ASD, even though the crystalline excipient stabilizes the polymer-free API. Consequently, excipients should be evaluated based on the thermodynamic phase behavior of the individual mixture of API/polymer/excipient, rather than based on pure-component properties of the excipient only. In-silico predictions proposed in this work remarkably decrease the number of screening tests for identifying suitable formulation excipients.

The progress on sulfhydryl modified polymers with regard to synthesis, characterization and mucoadhesion.

The concepts of mucoadhesion and mucoadhesive polymers were introduced in the 20th century, leading to several advantages. These included enhanced drug absorption and extended residence at specific site of action. Polymeric excipients underwent chemical modification with sulfhydryl groups on the polymeric backbone so as to improve mucoadhesive features as well as potential. This modification resulted in compounds mimicking the nature of secreted mucus glycoproteins. Thus, these thiol group-bearing excipients presented the ability to attach covalently to the mucosa by the disulfide bonding. Nevertheless, the first generation of these thiol-modified polymers, named thiomers, presented disadvantages such as low stability in aqueous media and/or the high susceptibility towards oxidation along with the drawback of low sufficient reactive functional moieties on the polymeric backbone at lower pH. Therefore, in the 21st century, a second generation of preactivated or S-protected polymers with protected thiol moieties were developed, as well as a third generation of thiomers, solving some of the previously described problems. This review article aimed to highlight the progess on a potent sulfhydryl modification during the last decades and the posterior characterization and in vitro/ex vivo/in vivo mucoadhesiveness.

Role of Polymer Excipients in the Kinetic Stabilization of Drug-Rich Nanoparticles.

Amorphous solid dispersions (ASDs) of crystallizable drugs and polymer excipients are attractive for enhancing the solubility and bioavailability of hydrophobic drug molecules. In this study, the solution behavior of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PND) and poly(vinylpyrrolidone-co-vinylacetate) (PVPVA), as polymer excipients, and nilutamide (NLT), phenytoin (PHY), and itraconazole (ITN) as model drugs, were monitored by an in vitro dissolution assay, small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), and polarized optical microscopy (POM). High degrees of drug supersaturation were coincident with the formation of amorphous nanoparticles in each system. The difference in particle size and kinetic stability between PND and PVPVA systems suggest a difference in how the polymers interact with the drug-rich phase. A series of scenarios are proposed based on whether the polymer interacts more strongly with the drug-rich nanoparticles or with water. Understanding the contribution of drug-rich nanoparticles to achievable supersaturation and the effect of polymer excipients on these particles will inform the design of future solid dispersion systems through a better understanding of the polymer/drug solution relationship.

Design and Development of Propranolol Hydrochloride Transdermal Patches: In Vitro and Ex Vivo Characterization

The main aim of this investigation is to design and develop matrix type transdermal patches of Propranolol Hydrochloride which is an anti-hypertensive drug. These matrix type transdermal patches were prepared by “Solvent Casting Technique” using drug, HPMC E15 and Eudragit L 100 in the ratio of 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5. All formulations carried 20%v/w of PEG-600 as plasticizer. The prepared patches were characterized for various physicochemical parameters like weight, thickness, folding endurance, drug content, percent moisture content, percent moisture absorption, in vitro drug release and ex vivo permeation. Among this 1:9 ratio was found to be an Optimized formulation and patches were prepared by using permeation enhancers (lemon grass oil, Eucalyptus oil, and clove oil). The cumulative amount of drug release in 12hrs for F7 formulation showed maximum and used for that formulation skin permeation on Goat abdominal skin. FTIR studies show no interaction between drug, polymer and other excipients. The drug permeation kinetics followed “First order” and “zero order” profile with diffusion mechanism.

Comparative Study of the Mucoadhesive Properties of Polymers for Pharmaceutical Use

BACKGROUND: In recent years, mucoadhesive dosage forms due to their advantages have attracted the interest of researchers and developers. Polymeric excipients are included into the drug composition to give adhesion to the mucous membrane.
 AIM: The aim of this research was to select a specific brand of pharmaceutical quality polymer that is promising for inclusion in the drug formulation.
 METHODS: The article presents the results of studying the mucoadhesive properties of polymers on two models using mucin: By measuring the amount of adhesion and by the evaluation the sample movement speed.
 RESULTS: According to the combination of two indicators, the highest mucoadhesive properties were shown by the brands of hydroxypropylmethylcellulose and xanthan gum. In addition, it was noted that hydroxyethylcellulose (HEC), sodium alginate, and hydroxypropylmethylcellulose (HPMC) also have good mucoadhesive properties. Polyethylene glycols proved to have the weakest mucoadhesive properties. The negative relationship between the average molecular weight and the sample movement speed of the HEC and HPMC was established. Obtained data showed no direct influence of the polymer average molecular weight on the amount of adhesion. It was also noted that there is no strong correlation between the amount of adhesion and the sample movement speed of the experimental samples.
 CONCLUSION: Based on the results of the study, it was suggested that the complex influences of the physical and chemical properties of the polymer on its mucoadhesive properties.

The preparation of felodipine/zein amorphous solid dispersions and in vitro evaluation using a dynamic gastrointestinal system

ABSTRCT Felodipine has been widely used as a poorly water-soluble model drug for various studies to improve its oral bioavailability and in vivo efficacy. In this study, we developed amorphous solid dispersions (ASDs) via spray drying to enhance the bioavailability of felodipine through using natural zein protein as a novel polymeric excipient. The solid state characterization results demonstrated a single glass transition temperature (Tg ) around 128.6 °C and good physical stability post 3 months accelerated study under the condition of 40 °C and 75% relative humidity (RH), which is possibly accounted for the molecular immobilization and hydrogen bonding interactions between felodipine and zein. By combining the in vitro dissolution study with TIM-1 gastrointestinal simulation investigation, it is indicated that felodipine was rapidly released from the ASD in 30 mins, and the supersaturation of felodipine was well maintained over 6 h, which resulted in a significant enhancement of felodipine bioavailability during simulated digestive processes in the upper GI tract. This study suggests that spray drying combined with natural excipient zein is an efficient formulation strategy for the development of ASDs with enhanced aqueous solubility and bioavailability.

Thiolated PVP-Amphotericin B Complexes: An Innovative Approach toward Highly Mucoadhesive Gels for Mucosal Leishmaniasis Treatment.

The aim of this study was to synthesize polymeric excipients that can form mucoadhesive hydrogels containing amphotericin B (AmB) for the treatment of mucosal leishmaniasis. 2-(2-Acryloylaminoethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinyl pyrrolidone to obtain thiolated polyvinylpyrrolidone (PVP) that was then complexed with AmB to improve its solubility. The resulting structure of thiolated PVP was evaluated by 1H nuclear magnetic resonance to confirm S-protected thiol groups, and the average molecular mass was determined by size exclusion chromatography. Moreover, variants of thiolated PVP-AmB were studied for the thiol content, amount of complexed AmB, cytotoxicity, mucoadhesive properties, and antileishmaniasis activity. The highest achieved degree of thiolation was 772 ± 24.64 μmol/g, and the amount of complexed AmB was 27.05 ± 0.31 μmol per g of polymer. Thiolated PVP and thiolated PVP-AmB variants (0.5% m/v) showed no cytotoxicity, whereas the equivalent concentration of free AmB reduced Caco-2 cell viability to 70% within 24 h. Thiol-functionalized PVP and PVP-AmB complexes displayed 7.66- and 7.20-fold higher adhesion to the mucosal surface in comparison to unmodified PVP and PVP-AmB, respectively. In addition, variants of thiolated PVP-AmB complexes displayed 100% antileishmaniasis activity in comparison to the 80% killing efficiency of Fungizone, which has been applied in the equivalent AmB concentration of 0.2 μg/mL. Thiol-functionalized PVP proved to be a promising novel excipient for the delivery of AmB providing enhanced solubility and improved mucoadhesive properties which are beneficial for the treatment of mucosal leishmaniasis.

Nanosuspensions of a poorly soluble investigational molecule ODM-106: Impact of milling bead diameter and stabilizer concentration.

Aqueous solubility of a drug substance is an important attribute affecting oral bioavailability. Nanonization, particle size reduction to submicron level, is an elegant approach to improve drug solubility and dissolution by increasing the surface energy, which in turn necessitates the use of stabilizers. The purpose of this study was to develop a nanosuspension of a practically water-insoluble investigational molecule by nanomilling approach using wet media milling. A variety of polymeric and surface active excipients were tested for their wettability. A combination of hydroxypropyl methylcellulose and sodium lauryl sulfate (SLS) were selected as stabilizers on the bases of compatibility studies and efficient wettability behaviour in contact angle measurements (≈80˚). A factorial design set-up was used to study the effect of milling bead diameter and stabilizer concentration on the efficiency of particle size reduction. Nanonization outcome was different when milling beads of 0.5mm and 1mm diameter were used at different concentrations of the stabilizers, which demonstrated the complex nature of the whole system. Storage of the nanosuspensions under different temperature conditions resulted only in minor changes of the particle size fractions.

An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients.

Insulin has been used to treat diabetes for almost 100 years; yet, current rapid-acting insulin formulations do not have sufficiently fast pharmacokinetics to maintain tight glycemic control at mealtimes. Dissociation of the insulin hexamer, the primary association state of insulin in rapid-acting formulations, is the rate-limiting step that leads to delayed onset and extended duration of action. A formulation of insulin monomers would more closely mimic endogenous postprandial insulin secretion, but monomeric insulin is unstable in solution using present formulation strategies and rapidly aggregates into amyloid fibrils. Here, we implement high-throughput-controlled radical polymerization techniques to generate a large library of acrylamide carrier/dopant copolymer (AC/DC) excipients designed to reduce insulin aggregation. Our top-performing AC/DC excipient candidate enabled the development of an ultrafast-absorbing insulin lispro (UFAL) formulation, which remains stable under stressed aging conditions for 25 ± 1 hours compared to 5 ± 2 hours for commercial fast-acting insulin lispro formulations (Humalog). In a porcine model of insulin-deficient diabetes, UFAL exhibited peak action at 9 ± 4 min, whereas commercial Humalog exhibited peak action at 25 ± 10 min. These ultrafast kinetics make UFAL a promising candidate for improving glucose control and reducing burden for patients with diabetes.

How Does the CO2 in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide?

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO2 in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser diffraction measurements. Differential scanning calorimetry was applied to assess thermal properties, while X-ray powder diffractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO2 led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release.

The tangential flow absorption model (TFAM) – A novel dissolution method for evaluating the performance of amorphous solid dispersions of poorly water-soluble actives

There is a substantial demand for absorptive dissolution tests, as single vessel dissolution experiments were originally not designed for testing supersaturating systems. Current approaches suffer from inadequate mass transfer of the dissolved active from the dissolution site, discrepancies in the fluid volume compared to in vivo intestinal fluid volumes or the dilution of functional excipients.In this work a novel dissolution apparatus was developed that enables adjustable mass transfer of the active through a membrane, while retaining the functional polymeric excipients at the dissolution site. Using this setup the dissolution behavior of various spray dried amorphous solid dispersions containing carbamazepine, hydrochlorothiazide and ketoconazole as model actives at intermediate and high supersaturation levels was evaluated. Compared to non-absorptive dissolution experiments, differences in the concentration-time profiles were noted. The experiments with a high supersaturation of ketoconazole revealed a concentration decrease over time under absorptive conditions. Additionally, it was observed that the difference between “spring” as well as “spring and parachute” formulations was less pronounced with increasing drug efflux. Further, the apparatus was also tested with Fasted State Simulated Intestinal Fluid as dissolution medium and results were compared to phosphate buffer pH6.8. As major benefits of the new TFAM apparatus the easy experimental procedure and sample preparation for drug concentration measurements using spectroscopy in the permeate, without the necessity for additional filtration and/or centrifugation to remove precipitated drug molecules, could be highlighted. This TFAM approach seems to be a promising tool for identifying formulations for amorphous solid dispersions with optimal in vitro performance.

Enhancement of the Physical Stability of Amorphous Sildenafil in a Binary Mixture, with either a Plasticizing or Antiplasticizing Compound.

The main purpose of this paper was to evaluate the impact of both high- and low-Tg polymer additives on the physical stability of an amorphous drug, sildenafil (SIL). The molecular mobility of neat amorphous SIL was strongly affected by the polymeric excipients used (Kollidon VA64 (KVA) and poly(vinylacetate) (PVAc)). The addition of KVA slowed down the molecular dynamics of amorphous SIL (antiplasticizing effect), however, the addition of PVAc accelerated the molecular motions of the neat drug (plasticizing effect). Therefore, in order to properly assess the effect of the polymer on the physical stability of SIL, the amorphous samples at both: isothermal (at constant temperature—353 K) and isochronal (at constant relaxation time—τα = 1.5 ms) conditions were compared. Our studies showed that KVA suppressed the recrystallization of amorphous SIL more efficiently than PVAc. KVA improved the physical stability of the amorphous drug, regardless of the chosen concentration. On the other hand, in the case of PVAc, a low polymer content (i.e., 25 wt.%) destabilized amorphous SIL, when stored at 353 K. Nevertheless, at high concentrations of this excipient (i.e., 75 wt.%), its effect on the amorphous pharmaceutical seemed to be the opposite. Therefore, above a certain concentration, the PVAc presence no longer accelerates the SIL recrystallization process, but inhibits it.