Drug In Polymer Matrix Research Articles

Co-precipitates of lumefantrine-Eudragit E PO for dissolution improvement

Lumefantrine, an antimalarial drug, is having poor solubility and variable bioavailability. This work is aimed to prepare and evaluate co-precipitate of lumefantrine-Eudragit E PO to improve its dissolution by anti-solvent precipitation. The anti-solvent precipitation technique was used to prepare co-precipitate of lumefantrine-Eudragit E PO at different ratios and based on their solubility; the optimized ratio (1:0.5) was further evaluated for solid state characterization, dissolution and compared with lumefantrine and pure precipitated lumefantrine. The optimized ratio of co-precipitate (1:0.5) was further evaluated which showed a substantial rise in drug solubility of lumefantrine. SEM photographs indicated dispersion of drug in polymer matrix however, no interaction was observed in FTIR studies. Their DSC and XRPD data revealed the conversion of lumefantrine to its amorphous form. Further, a significant improvement in the rate of dissolution was demonstrated by co-precipitate as compare to pure drug or solely precipitated drug. This may be attributed to the partial conversion of lumefantrine in amorphous form and solubilizing capacity of Eudragit E PO. Thus, co-precipitate of lumefantrine-Eudragit E PO was found to be useful in dissolution improvement and can be further studied for stabilization of co-precipitates.

Fabrication of chitosan-alginate polyelectrolyte complexed hydrogel for controlled release of cilnidipine: a statistical design approach

In the present investigation, fabrication and statistical optimization of chitosan-alginate polyelectrolyte complex (PEC) beads were performed for controlled delivery of Cilnidipine (CIL). PEC beads containing CIL were prepared by ionic cross-linking with calcium chloride. A statistical optimization was performed by employing a 32 full factorial design. Graphical optimization using overlay plot provides optimum combination of both the factors with the desired ranges of response. The optimum formulation of CIL (CB-O) was developed employing sodium alginate (2·2%w/v) and chitosan (1·2% w/v). CB-O formulation showed particle size (mm) =1·62 ± 0·42; DEE (%) = 90·21 ± 1·66; and drug release (%) = 89·58 ± 1·93; furthermore, solid state characterization by DSC, SEM, and XRD analysis reveals uniform dispersion of drug in polymer matrix. Controlled release CIL beads may find future perspectives in enhancing patient compliance by the abrupt reduction in side effects and dose frequency owing to effective therapeutic efficacy as indicated by the in-vitro study.

Dissolution rate enhancement of irbesartan and development of fast-dissolving tablets

ObjectiveThe objective of the present investigation was to enhance the solubility and dissolution rate of poorly soluble drug irbesartan by preparing it as solid dispersions and formulating it as fast-dissolving tablets (FDTs) using various excipients.BackgroundIrbesartan is poorly soluble in water, and this low aqueous solubility in addition to its poor wettability leads to poor bioavailability of the drug.Materials and methodsSolid dispersions were prepared using Soluplus, PEG 6000, and Kollidon as carriers. The dispersions were prepared using the solvent evaporation and kneading methods in a 1:1 ratio of drug and carrier. These formulations were characterized for solid state properties using X-ray powder diffraction and Fourier transform infrared spectroscopy spectral studies. Formulations were further evaluated for dissolution.ResultsThe aqueous solubility of irbesartan in solid dispersions was improved by the presence of polymer Soluplus when compared with other carriers. Solid state characterization indicated that irbesartan was present as amorphous material in the formulation with carrier. This was due to efficient entrapment of the drug in polymer matrix. Thus, the solid dispersion prepared with Soluplus would be useful for delivering poorly soluble irbesartan with enhanced solubility and dissolution rate. Furthermore, the solid dispersions that were formulated as FDTs using superdisintegrants showed faster drug release with increased dissolution rate.ConclusionFDTs containing irbesartan solid dispersions prepared using the solvent evaporation method and croscarmellose sodium as superdisintegrant showed faster disintegration and increased dissolution rate.

Synthesis and characterization of biocompatible polyurethanes for controlled release of hydrophobic and hydrophilic drugs

Design of biocompatible and biodegradable polymer systems for sustained and controlled release of bioactive agents is critical for numerous biomedical applications. Here, we designed, synthesized, and characterized four polyurethane carrier systems for controlled release of model drugs. These polyurethanes are biocompatible and biodegradable because they consist of biocompatible poly(ethylene glycol) or poly(caprolactone diol) as soft segment, linear aliphatic hexamethylene diisocyanate or symmetrical aliphatic cyclic dicyclohexylmethane-4,4′-diisocyanate as hard segment, and biodegradable urethane linkage. They were characterized with Fourier transform infrared spectroscopy, atomic force microscope, and differential scanning calorimetry, whereas their degradation behaviors were investigated in both phosphate buffered saline and enzymatic solutions. By tuning polyurethane segments, different release profiles of hydrophobic and hydrophilic drugs were obtained in the absence and presence of enzymes. Such difference in release profiles was attributed to a complex interplay among structure, hydrophobicity, and degradability of polyurethanes, the size and hydrophobicity of drugs, and drug-polymer interactions. Different drug-polyurethane combinations modulated the distribution and location of the drugs in polymer matrix, thus inducing different drug release mechanisms. Our results highlight an important role of segmental structure of the polyurethane as an engineering tool to control drug release.

Transcorneal permeation of diclofenac as a function of temperature from film formulation in presence of triethanolamine and benzalkonium chloride

The objective of this report was to evaluate the transcorneal permeation of diclofenac potassium (DCP) as a function of temperature from hydroxypropyl methylcellulose (HPMC) matrix film containing triethanolamine (TEM) as plasticizer and benzalkonium chloride (BKC) as preservative. Activation energy (Ea), enthalpy (ΔH), entropy (ΔS) and free energy (ΔG) of permeation, diffusion and partition were evaluated to understand the underlying mechanism of permeation. Permeation improved with the presence of both the plasticizer and preservative compared to preservative alone. Further, increased amount of TEM in the film increased drug transport across the cornea. Decreased Ea value of the film supported the fact. Rise of temperature from 26 to 30, 34 and 40°C increased permeation in all the films. Ocular residence of the film in vivo in the rabbit revealed that the film swelled by pronounced lachrymal fluid uptake and traces of hydrogel remained still at the end of 6h of application. Absence of characteristic exothermic peak of the drug in the thermogram of film formulations indicated the molecular dispersion of drug in polymer matrix. Scanning electron microscopy indicated that the drug crystal size decreased with increasing concentration of TEM in presence of BKC due to effective wetting of drug particles by the polymer.

Polyvinylpyrrolidone oral films of enrofloxacin: film characterization and drug release.

Enrofloxacin is a fluoroquinolone derivative used for treating urinary tract, respiratory and skin infections in animals. However, low solubility and low bioavailability prevented it from using on humans. Polyvinylpyrrolidone (PVP) is an inert, non toxic polymer with excellent hydrophilic properties, besides it can enhance bioavailability by forming drug polymer conjugates. With the aim of increasing solubility and bioavailability, enrofloxacin thin films were prepared using PVP as a polymer matrix. The obtained oral thin films exhibited excellent uniformity and mechanical properties. Swelling properties of the oral thin films revealed that the water uptake was enhanced by 21%. The surface pH has been found to be 6.8±0.1 indicating that these films will not cause any irritation to oral mucosa. FTIR data of the oral thin films indicated physical interaction between drug and polymer. SEM analysis revealed uniform distribution of drug in polymer matrix. In vitro drug release profiles showed enhanced release profiles (which are also pH dependant) for thin films compared to pure drug. Antibacterial activity was found to be dose dependent and maximum susceptibility was found on Klebsiella pneumonia making this preparation more suitable for respiratory infections.

Lean Raman Imaging for Rapid Assessment of Homogeneity in Pharmaceutical Formulations

Solid dispersion formulations and drug in polymer matrices are increasingly being used by the pharmaceutical industry to enhance the solubility, or bio-availability, of active pharmaceutical ingredients (APIs). The degree of solubility or bio-availability enhancement, as well as properties such as chemical stability and physical characteristics, will be dependent on the homogeneity of the drug in polymer matrix. The use of Raman spectroscopy to assess homogeneity has traditionally been limited by the time required to acquire images from a statistically representative sample area. This may be overcome by employing a more rapid one-dimensional Raman line-mapping approach and using a statistical analysis to extract the critical information. This approach has been termed "lean" Raman imaging and allows a large area of sample to be probed in a relatively short space of time. This paper discusses the use of "lean" Raman imaging to assess two performance-indicating parameters of a drug in polymer formulation, sedimentation of the API within a capsule formulation and phase separation of the individual components. The development of a screening method, using Raman line mapping to allow rapid measurement of sedimentation of the API, is discussed. This method requires less than half an hour per capsule for data collection and processing. In addition, the development of a "lean" Raman mapping technique, using single line scans to assess drug and polymer domain sizes, is detailed. This technique employs a simple peak ratio approach coupled with statistical analysis to provide a measure of the degree of drug and polymer segregation without the need for acquisition of high pixel density images or multivariate analysis. The Raman mapping data is compared with both the dissolution profiles and processing parameters of the samples tested and a strong correlation is shown between formulation homogeneity and dissolution behavior.

Modeling the controlled release of drug embedded in a plate-like polymer matrix

The controlled release of over-loaded drug in a plate-like polymer matrix, the Higuchi's problem, is investigated theoretically. Taking the advantage of Landau transformation, we restore the concentration profile of drug in a polymer matrix, the rate of release of drug from the polymer matrix, and the temporal variation of location of the moving boundary taking the external mass transfer resistance into account. The applicability of the series of moving boundaries, a numerical approach often adopted, is examined. We found that it may become ineffective when the over-loading of drug in a polymer matrix is too small. In contrast, our method has no such limitation. We conclude that assuming the transfer of drug to occur at a pseudo-steady-state condition is inadequate if the degree of over-loading for drug is low or the external mass transfer resistance is significant.

The Effect of Storage Temperatures on the In Vitro Properties of a Polyanhydride Implant Containing Gentamicin

ABSTRACTSeptacin® is a biodegradable sustained-release implant containing 20% (w/w) gentamicin sulfate. The matrix of the implant is a polyanhydride copolymer composed of erucic acid dimer (EAD) and sebacic acid (SA) in a one-to-one weight ratio. The effect of storage temperatures (−15°C and 25°C) on the stability of Septacin® was evaluated with respect to gentamicin potency, copolymer molecular weight, and in vitro drug release. The drug in polymer matrix was stable for at least 12 months when stored at 25°C, but the molecular weight of the copolymer declined rapidly at this temperature. At −15°C, there was no change in the molecular weight of the copolymer. However, the placebo (copolymer without gentamicin) exhibited a significant drop in copolymer molecular weight at both temperatures. The drug release profiles showed no change for samples stored at −15°C for the duration of this study, while the release of drug slowed down significantly for samples stored at 25°C for longer than one month. A pronounced difference in the morphology of the −15°C samples and the 25°C samples was observed during the in vitro dissolution test; cracking of the −15°C samples was evident, but the 25°C samples remained intact.

Regularities of Multicomponent Transport in Polymer Systems for Controlled Drug Release

Abstract A mathematical model predicting the behavior of systems consisting of hydrophylic polymer, water, and a low-molecular compound has been developed. The model takes into account the process of swelling of polymers during water sorption, the existence of the embedded form of drug in polymer matrix and some other factors. The dependence of physico-chemical parameters on concentration of water, drug and on mechanical properties of polymer were confirmed by corresponding experimental results. Different ratios of kinetic parameters determined in this study enable us to predict the effect of matrix characteristics on controlled release of drugs.

The Modeling of the Simultaneous Transport of Solvent and Low-Molecular Compounds in Swelling Polymers

Abstract Mathematical model has been developed in order to predict the behavior of systems consisting of hydrophylic polymer, water, and low-molecular compound. The model has taken into account the processes of swelling of polymers during water sorption. the existence of embedded form of drug in polymer matrix and some others processes. The dependencies of physico-chemical parameters on concentration of water, drug and on mechanical properties of poiymer were justified by corresponding experimental results. Different ratios of these parameters enable to predict the behavior of matrix systems for controlled release of drugs.