Release Of Active Pharmaceutical Ingredients Research Articles

Comprehensive study for the development of rectal suppositories with diosmin and hesperidin

The aim. To conduct a comprehensive study of biphasic-type suppositories that contain diosmin and hesperidin.
 Materials and methods. Samples of biphasic-type suppositories with a mass of 4.0 were objects of the study. Pharmacological, technological and analytical research methods were used to directly or indirectly analyze the strength and completeness of the drug activity. Thus, in this work we combined the study of the specificity of the pharmacological action of the drug, experimental verification of the quantitative content of API, analysis of the structural properties of suppositories and study of the profile of the release of active pharmaceutical ingredients.
 Results. Therefore, based on the obtained data, the most effective dose was 75 mg / kg (in terms of a human dose of 300 mg per suppository). The drug in the selected dose showed a significant therapeutic effect, which significantly exceeded that of the test sample at a lower dose and the reference agent. According to the results of technological studies, it was determined that all samples of suppositories had satisfactory structural and mechanical properties. Studies of the histological structure of the mucous membrane of rats proved that there is a positive effect of treatment with suppositories with diosmin and hesperidin due to the improvement of the normal condition of the mucous membrane, the absence of edema and ulcerative defect. Research of the release profile of active pharmaceutical ingredients showed that the best percentage of release is characteristic of sample 2 (99.8 %)
 Conclusions. Therefore, suppositories with diosmin and hesperidin in therapeutically dose of 75 mg/kg of animal weight can be used for further research and will be of interest in the treatment of hemorrhoids of both acute and chronic forms

Osmotic tablet coatings: Drying stress, mechanical properties and microstructure

The coatings in osmotic tablets play a critical role in controlling the release of active pharmaceutical ingredient. Coatings are formed by spraying dilute polymer solution onto the tablet surface. During drying, the films develop shrinkage stress, which can cause cracking. The coatings are also subject to large tensile stress generated by osmotic pressure during the dissolution process, which may rupture the coating. Despite the role of tensile stress in causing fracture in osmotic tablet coatings, a rigorous quantification of the drying stress, mechanical properties and microstructure is missing. The present work fills this gap via detailed measurement of drying stress, Young’s modulus and fracture properties of osmotic tablet coatings of cellulose acetate mixed with two different plasticisers, namely polyethylene glycol and hydroxypropyl cellulose. The measurements were complemented with imaging of the surface and the cross-section of films using scanning electron microscopy so as to relate the drying stress and mechanical properties to the microstructure of the films. The phase separation during the drying process increases the pore size, while simultaneously decreasing the modulus and the peak drying stress of the drying films. The results suggest that films with strong adhesion to the tablet surface will not rupture but if the films delaminate, the drying stress are sufficiently large to cause rupture. The detailed study presented here provides guidelines to the formulator for designing rupture-free osmotic coatings.

Simultaneous Determination of Active Pharmaceutical Ingredients and Water-Soluble Polymers: Analysis of Dissolution Profiles from Sustained-Release Formulations and Mechanisms Involved.

The dissolution behaviors of base excipients from sustained-release formulations have been investigated using various methodologies. However, the dissolution of polymers has not been fully evaluated because differences between formulations are still verified only by the release of active pharmaceutical ingredients (APIs). In our previous study, we proposed a quick and simultaneous analysis of dissolved APIs and water-soluble polymers by ultra HPLC using charged aerosol and photodiode array detectors. The purpose of this study was to verify whether the analysis system could be adapted to other water-soluble polymers. Dissolution tests were conducted using matrix model tablets prepared from three polymers and three APIs (propranolol, ranitidine, and cilostazol) with different solubilities. The dissolution profiles of the polymers and APIs were determined using the proposed analysis system and compared. The results clarified differences in the dissolution behaviors of the APIs and polymers. The polymers, especially hydroxypropyl cellulose, exhibited the dissolution properties characteristic of each model formulation. Propranolol and ranitidine showed the diffusion type, while cilostazol showed the erosion type release mechanism due to their different solubilities. The release of cilostazol was delayed in all models compared to the polymer, which may be due to the aggregation of cilostazol in the gel layer. This analytical method can be used to study the dissolution behavior (diffusion or erosion) of APIs from matrix tablets containing various polymers. This method will provide useful information on release control, which will make it easier and more efficient to design appropriate formulations and analyze the release mechanisms.

Hydrogel Microparticle-Templated Anti-Solvent Crystallization of Small-Molecule Drugs.

Conventional formulation strategies for hydrophobic small-molecule drug products frequently include mechanical milling to decrease active pharmaceutical ingredient (API) crystal size and subsequent granulation processes to produce an easily handled powder. A hydrogel-templated anti-solvent crystallization method is presented for the facile fabrication of microparticles containing dispersed nanocrystals of poorly soluble API. Direct crystallization within a porous hydrogel particle template yields core-shell structures in which the hydrogel core containing API nanocrystals is encased by a crystalline API shell. The process of controllable loading (up to 64% w/w) is demonstrated, and tailored dissolution profiles are achieved by simply altering the template particle size. API release is well described by a shrinking core model. Overall, the approach is a simple, scalable and potentially generalizable method that enables novel means of independently controlling both API crystallization and excipient characteristics, offering a "designer" drug particle system.

Data-Enriched Edible Pharmaceuticals (DEEP) with Bespoke Design, Dose and Drug Release.

Data-enriched edible pharmaceuticals (DEEP) is an approach to obtain personalized medicine, in terms of flexible and precise drug doses, while at the same time containing data, embedded in quick response (QR) codes at a single dosage unit level. The aim of this study was to fabricate DEEP with a patient-tailored dose, modify drug release and design to meet patients’ preferences. It also aimed to investigate physical stability in terms of the readability of QR code patterns of DEEP during storage. Cannabinoids, namely, cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), were used as the model active pharmaceutical ingredients (APIs). Three different substrates and two colorants for the ink were tested for their suitability to fabricate DEEP by desktop inkjet printing. Flexible doses and customizable designs of DEEP were obtained by manipulating the digital design of the QR code, particularly, by exploring different pattern types, embedded images and the physical size of the QR code pattern. Modification of the release of both APIs from DEEP was achieved by applying a hydroxypropyl cellulose (HPC) polymer coating. The appearance and readability of uncoated and polymer-coated DEEP did not change on storage in cold and dry conditions; however, the HPC polymer layer was insufficient in preserving the readability of the QR code pattern in the extreme storage condition (40 °C and 75% relative humidity). To sum up, the DEEP concept provides opportunities for the personalization of medicines, considering also patients’ preferences.

Cellular Automata Modeling of Three-Dimensional Chitosan-Based Aerogels Fiberous Structures with Bezier Curves.

In this work, a cellular automata approach was investigated for modeling three-dimensional fibrous nanoporous aerogel structures. A model for the generation of fibrous structures using the Bezier curves is proposed. Experimental chitosan-based aerogel particles were obtained for which analytical studies of the structural characteristics were carried out. The data obtained were used to generate digital copies of chitosan-based aerogel structures and to assess the accuracy of the developed model. The obtained digital copies of chitosan-based aerogel structures will be used to create digital copies of aerogel structures with embedded active pharmaceutical ingredients (APIs) and further predict the release of APIs from these structures.

Particle-based coarse-grained approach for simulating dry powder inhaler

Drug delivery via dry powder inhaler (DPI) is a complex process affected by multiple factors involving gas and particles. The performance of a carrier-based formulation depends on the release of active pharmaceutical ingredient (API) particles, typically characterized by fine particle fraction (FPF) and dispersion fraction (DF). Computational Fluid Dynamics coupled with Discrete Element Method (CFD-DEM) can capture relevant gas and particle interactions but is computationally expensive, especially when tracking all carrier and API particles. This study assessed the efficacy of two coarse-grained CFD-DEM approaches, the Discrete Parcel Method and the representative particle approach, through highly-resolved CFD-DEM simulations. The representative particle approach simulates all carrier particles and a subset of API particles, whereas the Discrete Parcel Method tracks parcels representing a specified number of carrier or API particles. Both approaches are viable for a small carrier-API size ratio which requires modest degrees of coarse-graining, but the Discrete Parcel Method showed limitations for a large carrier-API size ratio. The representative particle approach can approximate CFD-DEM results with reasonable accuracies when simulations include at least 10 representative API particles per carrier. Using the representative particle approach, we probed powder characteristics that could affect FPF and DF in a model problem and correlated these fractions with the maximum carrier-API cohesive force per unit mass of API particles.

Modular solid dosage form design – Application to pH-independent release of a weak-base API

A novel approach to solid dosage form design is investigated, whereby instead of blending the ingredients and subsequently compacting the mixture, the dosage form is made by assembling prefabricated components, each with a specific function. The approach was used to formulate a weak-base API (active pharmaceutical ingredient), such that the modular dosage forms exhibited pH-independent drug release. Tablet-like dosage forms of ciprofloxacin (CPR), used as model weak-base drug, were prepared in order to generate dosage forms exhibiting pH-independent drug release. The dosage forms were made by assembling two types of prefabricated modules onto 3D stacks. The modules were hydroxypropyl methylcellulose circular film wafers, loaded with either CPR or citric acid (CA). CA-wafers served the function of pH-modifier modules in the microenvironment of the dosage form during the dissolution process. In vitro drug release from dosage forms consisting of CA- and CPR-wafers stacked in alternate sequence was compared with the release from assemblies containing CPR-wafers only, under pH = 1.2 and pH = 6.8 conditions. In the absence of CA-wafers, CPR release was ~25-fold slower at pH = 6.8 compared to pH = 1.2. Inclusion of CA-wafers in the dosage form assembly accelerated and decelerated drug release at pH = 6.8 and pH = 1.2, respectively, which resulted in overlapping drug release profiles under the two pH conditions. The two drug release profiles met the criteria for sameness as assessed by the f1 (difference) and f2 (similarity) factors. Modeling of drug release kinetics pointed toward polymer erosion as the primary mechanism of drug release for the overlapping pH = 1.2 and pH = 6.8 profiles. In terms of their drug release properties, the multi-modular dosage form assemblies exhibited the attributes and behavior of single bodies, rather than the combined contributions from multiple individually-operating modules. The initial geometry of the dosage form, characterized by the surface area (SA), volume (V) and SA/V ratio accounted for drug release kinetics in the same fashion as for traditional tablet compacts.

An overview on various types of gastroretentive drug delivery system

Gastro retentive drug delivery system is one of the approaches to achieve controlled drug delivery. The gastro retentive drug delivery system is a way to prolong residence time of active pharmaceutical ingredient in gastrointestinal tract. It is also applied for targeting drug in upper gastrointestinal tract for generating local and systemic effect. Controlled drug delivery creates a window of absorption that release drug for a longer duration of time before reaching absorption site. Gastro retentive drug delivery systems have gained wide variation of oral drug distribution in the area of late. It includes all the approaches that keep the dosage form in the stomach for a longer duration of time. This also enables sustained release of active pharmaceutical ingredient which in turn overcomes many limitations of conventional drug delivery systems. It has begun tremendous advances in the field of gastro-retention to meet controlled release of drugs. Aim of research. The main aim of this survey to prolong the gastric retention dosage form in the stomach and improve the medication concentration in the stomach. Material and Method. To prepare this manuscript, various keywords were searched in different search engines such as Google, Yahoo, Bing etc. The available information in public domain was collected and classified according to delivery system. This review paper aim to provide complete information about different delivery systems related to Gastro retentive drug delivery systems (GRDDS). It is also applied for targeting drug in upper gastrointestinal tract for generating local and systemic effect. Result. After going through various literatures, it can be said that the GRDDS can improve local bioavailability and therapeutic efficacy and dosing frequency possible reduction in dose size. This paper is focused on various physiological contemplation and obtainable formulation approaches for development of gastro retentive drug delivery system. Conclusions. This article discusses various types of GRDDS and their approaches. The gastric retentive drug delivery systems improve drug absorption. Prolonged gastric retention time of therapeutic mutations provide several benefits such as improving absorption, bioavailability and enhance the therapeutic action of drug

Co-delivery of inhalable therapies: Controlling active ingredients spatial distribution and temporal release

The management of respiratory diseases relies on the daily administration of multiple active pharmaceutical ingredients (APIs), leading to a lack of patient compliance and impaired quality of life. The frequency and dosage of the APIs result in increased side effects that further worsens the overall patient condition. Here, the manufacture of polymer-polymer core-shell microparticles for the sequential delivery of multiple APIs by inhalation delivery is reported. The microparticles, composed of biodegradable polymers silk fibroin (shell) and poly(L-lactic acid) (core), incorporating ciprofloxacin in the silk layer and ibuprofen (PLLA core) as the antibiotic and anti-inflammatory model APIs, respectively. The polymer-polymer core-shell structure and the spatial distribution of the APIs have been characterized using cutting-edge synchrotron macro ATR-FTIR technique, which was correlated with the respective API sequential release profiles. The APIs microparticles had a suitable size and aerosol properties for inhalation therapies (≤4.94 ± 0.21μm), with low cytotoxicity and immunogenicity in healthy lung epithelial cells. The APIs compartmentalization obtained by the microparticles not only could inhibit potential actives interactions but can provide modulation of the APIs release profiles via an inhalable single administration.

Adsorptive removal of vitamin B6 and ciprofloxacin using polyurethane foam in pure and pharmaceutical preparations: Kinetic and equilibrium studies

AbstractThe release of active pharmaceutical ingredients and their metabolites in surface waters and groundwater with insufficiently treated wastewaters nowadays may be a global environmental concern. In this study, simple, inexpensive, and solid phase procedure has been developed for the removal of pyridoxine hydrochloride (vitamin B6, PDX) and ciprofloxacin (CPX) onto polyurethane foam (PUF) using the batch mode technique. PUF was characterized using scanning electron microscopy and FT‐IR spectroscopy. The batch experiments indicated optimum conditions for the adsorption process at pH 5.6 for PDX and CPX. The optimum contact time to reach its best removal is 30 min for the removal of both drugs and the sorbent amount at 1.0 and 1.5 g for PDX and CPX, respectively. It was found that the experimental data for the adsorption of PDX fit well into Langmuir model with R2 values (0.979). Whereas the adsorption of CPX follows Freundlich model with R2 value (0.914). Adsorption process undergoes pseudo‐first‐order kinetic as proved by the high value of R2 (0.973) and (0.956) for PDX and CPX, respectively. Experimental results have proven that PUF has a great potential for the removal of both drugs with maximum removal efficiency 50 and 98% for PDX and CPX, respectively.

The Influence of pH Values on the Rheological, Textural and Release Properties of Carbomer Polacril® 40P-Based Dental Gel Formulation with Plant-Derived and Synthetic Active Components.

The physicochemical properties, especially pH value of dental medicines, have significant influence on the health of oral cavity tissues. The pH of formulations should correspond to the value of saliva pH (5.5–8.0). For carbomer-based gels, the required pH value is obtained by neutralizing them with alkaline components, which leads to their structuring (thickening). This affects the physical properties of the gel, its residence time at the application site and the rate of release of active pharmaceutical ingredient. Therefore, the main purpose of this study is to evaluate the rheological, textural, and biopharmaceutical properties of Carbomer Polacril® 40P-based dental gel depending on the pH value. Evaluation of the rheological properties of gel preparations were performed by measuring the structural viscosity of the samples as a function of pH and temperature. The textural properties of the gel were evaluated by performing tests regarding back extrusion and spreadability. Carbomer Polacril® 40P-based gels haven’t shown noticeable thixotropic behavior, and were characterized by plastic flow in the whole studied pH range. The structural viscosity at the selected average pH value hasn’t differed at storage (25 °C) and application (37 °C) temperature. Texture studies of dental gels have shown a strong correlation with rheoparameters. Their rheological behavior and textural properties haven’t changed significantly between the pH range of 5.5–6.6. The relatively narrow range of working pH values does not affect the change in the viscosity of the preparation significantly and, consequently, does not affect the release of APIs from the developed Carbomer Polacril® 40P-based dental gel.

Application of Dominance-Based Rough Set Approach for Optimization of Pellets Tableting Process.

Multiple-unit pellet systems (MUPS) offer many advantages over conventional solid dosage forms both for the manufacturers and patients. Coated pellets can be efficiently compressed into MUPS in classic tableting process and enable controlled release of active pharmaceutical ingredient (APIs). For patients MUPS are divisible without affecting drug release and convenient to swallow. However, maintaining API release profile during the compression process can be a challenge. The aim of this work was to explore and discover relationships between data describing: composition, properties, process parameters (condition attributes) and quality (decision attribute, expressed as similarity factor f2) of MUPS containing pellets with verapamil hydrochloride as API, by applying a dominance-based rough ret approach (DRSA) mathematical data mining technique. DRSA generated decision rules representing cause–effect relationships between condition attributes and decision attribute. Similar API release profiles from pellets before and after tableting can be ensured by proper polymer coating (Eudragit® NE, absence of ethyl cellulose), compression force higher than 6 kN, microcrystalline cellulose (Avicel® 102) as excipient and tablet hardness ≥42.4 N. DRSA can be useful for analysis of complex technological data. Decision rules with high values of confirmation measures can help technologist in optimal formulation development.

DEVELOPMENT OF THE EMULGE LFOR THE ANDROGENIC ALOPECIA TREATMENT

Androgenic alopecia (AGA) is the most common alopecia that is heritable, androgen-dependent and occurs in both sexes with defined patterns such as Male pattern hair loss in men and Female pattern hair loss in women. AGA affects at least 50 % of men by the age of 50 years, and up to 70 % of all males in later life. The aim.The research was aimed to substantiate the optimal concentration of excipients and active pharmaceutical ingredients (APIs) of the emulgel intended for the topical treatment of androgenic alopecia. Materials and methods. In this study the samples of the emulgel bases containing different carbomer Ultrez10 concentrationsin the range of 0.3–0.6 % and its neutralizers (0.1 % of potassium sorbate and 0 % or 0.2 % of triethanolamine) were used. Colloidal and thermal stability, pH, rheological properties (structural viscosity, mechanical stability, degree of thixotropy) of these samples were determined. The emulgel samples with different percentages of the Serenoa repens dry extract and the Sophora japonica tincture were used in the biopharmaceutical studies. The samples of the emulgel with the antioxidant butylhydroxytoluene different concentrations (0 %, 0.01 %, 0.02 %, 0.03 %) were used to determine acid value during 1 year of the emulgel storage. Results and discussion. It was experimentally substantiated the optimal ratio of the emulgel ingredients that provide good APIs release and necessary consumer properties of the semi-solid remedy like application compliance, safety and storage stability. Conclusions. Physicochemical, rheological and biopharmaceutical properties of emulgel bases have been studied. It was found that the base №2 (in which the concentrations of Carbomer Ultraz 10, potassium sorbate and triethanolamine are 0.3 %, 0.1 %, 0.2 % respectively) possessed the optimal properties. Considering the results of the complete range of experimental research it was developed the final formulation of the emulgel intended for AGA treatment which included the concentration of the APIs, neutralizers, preservatives, antioxidant and fragrance.

Microstructure based simulation of the disintegration and dissolution of immediate release pharmaceutical tablets

The design of pharmaceutical tablets involves the determination of formulation parameters that define the tablet composition and internal microstructure. These parameters must be chosen so that the release of an active pharmaceutical ingredient (API) from the tablet follows a prescribed dissolution curve. In the case of immediate release formulations, the dissolution process typically consists of tablet disintegration, followed by the dissolution of the disintegration fragments. In order to find the appropriate values of formulation parameters, numerous experiments are typically required. In the present work, we propose a computational methodology for in silico design of tablet formulations with the aim of reducing the amount experimental work required during tablet design. The methodology is based on the coupling of two modelling approaches: (i) tablet fragmentation triggered by the swelling of the disintegrant is simulated by the discrete element method (DEM), and (ii) the dissolution of the resulting population of disintegration fragments is simulated using a finite volume grid-based model. The final API release curve is then obtained by the superposition of dissolution curves originating from the individual disintegration fragments. Using directly compressed tablets containing ibuprofen as the API and croscarmellose sodium as the disintegrant, the model was validated against experimental data. The fragment size distribution was evaluated by static light scattering and the dissolution profiles were obtained by a standard dissolution apparatus with UV/Vis spectroscopic detection. We demonstrate that the computational methodology is able to quantitatively predict the effect of disintegrant content and API primary particle size on the fragment size distribution and the final dissolution profiles, and is therefore useful as a tool for computer-assisted tablet formulation design.

CFD approach for simulation of API release from solid dosage formulations

A comprehensive mathematical model has been developed to study release behaviour of Active Pharmaceutical Ingredients (API) from pharmaceutical solid dosage oral formulations. An analytical model was found in Dynochem resources and a numerical model was developed using COMSOL Multiphysics software using computational fluid dynamics based on finite element method in order to solve mass transfer equations. Only molecular diffusion was considered in the model to predict mass transfer of API molecules through the porous matrix. The model was developed in two steps; in the first step Dynochem was used to fit the data and find the unknown parameters. Then, COMSOL Multiphysics was used for prediction of API concentration over time. The experimental results were taken from the lab for release of Paracetamol from HPMC tablets, in order to validate the modelling process. The result of the study showed that both modelling methods are relatively good predictors of experimental values and that even models with limited complexity can serve this purpose well. The results can be used as predictive tools for designing novel drug controlled release systems.

Antibiotic eluting poly(ester urea) films for control of a model cardiac implantable electronic device infection

Cardiac implantable electronic device (CIED) infections acquired during or after surgical procedures are a major complication that are challenging to treat therapeutically, resulting in chronic and sometimes fatal infections. Localized delivery of antibiotics at the surgical site could be used to supplement traditional systemic administration as a preventative measure. Herein, we investigate a cefazolin-eluting l-valine poly(ester urea) (PEU) films as a model system for localized antibiotic delivery for CIEDs. Poly(1-VAL-8) PEU was used to fabricate a series of antibiotic-loaded films with varied loading concentrations (2%, 5%, 10% wt/wt) and thicknesses (40 µm, 80 µm, 140 µm). In vitro release measurements show thickness and loading concentration influence the amount and rate of cefazolin release. Group 10%-140 µm (load-thickness) showed 22.5% release of active pharmaceutical ingredient (API) in the first 24 h and 81.2% of cumulative percent release through day 14 and was found most effective in bacterial clearance in vitro. This group was also effective in clearing a bacterial infection in a model in vivo rat study while eliciting a limited inflammatory response. Our results suggest the feasibility of cefazolin-loaded PEU films as an effective sustained release matrix for localized delivery of antibiotics. Significance StatementImplant-associated infections acquired during surgical procedures are a major complication that have proven a challenge to treat clinically, resulting in chronic and sometimes fatal infections. In this manuscript, we investigate an antibiotic-eluting L-valine poly(ester urea) (PEU) films as a model system for localized delivery of cefazolin. Significantly, we demonstrate a wide variation in temporal delivery and dosing within this family of PEUs and show that the delivery can be extended by varying the film thickness. The in vivo results show efficacy in an infected wound model and suggest antibiotic loaded PEU films function as an effective sustained release matrix for localized delivery of antibiotics across a number of clinical indications.

Partial tablet coating by 3D printing.

In the last decade 3D printing (3DP) technology has gained increasing interest in the pharmaceutical field addressing several novel challenges such as on-demand manufacturing at the point of need, customization of drug release profiles and patient-specific solutions as well as combinations of several APIs in one dosage form. Therefore, 3DP can become a new and promising path to drug product development and manufacturing, able to support specific therapies and improve compliance, safety and effectiveness. The aim of this work was to partially coat tablets with a glyceride, namely Precirol ATO 5 using a semi-solids 3D printer as an approach for tuning the release of two Active Pharmaceutical Ingredients (APIs), the hydrophilic methyl-levodopa hydrochloride (Melevodopa) and the lipophilic Acyclovir. Various parameters of the 3DP coating process were purposefully modified using experimental design techniques in order to customize the selected APIs release profile, without affecting the core composition of the formulation. The percentage of the tablet surface coated, the number of coating layers as well as the coated sides of the tablet where the parameters which controlled the release profile for both APIs. Different dissolution profiles have been achieved by tuning these simple parameters, which revealed a non-Fickian release mechanism regardless of the API.

Amino Acid-Based Poly(ester urea)s as a Matrix for Extended Release of Entecavir

The use of polymers as excipients for drug delivery has afforded stable formulations that reliably control the release of active pharmaceutical ingredients (APIs). While many materials are available and used, few polymers exhibit the numerous advantages, including amorphous characteristics, noninflammatory properties, and resorbable degradation products, like those of poly(ester urea)s (PEUs). Furthermore, stability issues that arise in various APIs can make formulation optimization difficult. Herein, a series of PEUs were synthesized that vary by the fraction of l-phenylalanine monomer incorporated into the copolymerization. The various PEUs and entecavir monohydrate were dry-mixed at different weight percentages (15, 30, and 50%). Filaments of the PEU formulations were extruded and analyzed quantitatively for drug loading and content uniformity by using μ-CT and UPLC analysis. Drug dissolution profiles from filament segments were monitored over a 4-week period and ultimately showed that the controlled release of entecavir was influenced by the incorporation of the l-phenylalanine within the polymer.

Development of an emulgel for the treatment of rosacea using quality by design approach

Objective: The aim of this study was to develop an emulgel for the treatment of rosacea, applying quality by design (QbD).Methods: An emulgel designed to release the active pharmaceutical ingredients (APIs), metronidazole and niacinamide, via an emollient formulation that favors residence time and attenuates facial redness would be an excellent vehicle to develop to treat rosacea. It was decided to design first a vehicle presenting the attributes established in the quality target product profile, and then, after selecting the best formulation, to load the APIs in it to optimize the final emulgel. A design of experiments was introduced to study the effect of formulation variables on quality attributes (adhesion, phase separation by mechanical stress and viscosity) of the emulgels. Response surface methodology and desirability functions were applied for data analysis. After optimization, the final emulgel was further characterized by assay and in vitro release of APIs, attenuation of facial redness, and compared to commercially available metronidazole products regarding API release.Results: The final emulgel gradually released both APIs, reaching approximately 88% within the first 4 h, and their profiles were well described by the Higuchi model. Only a light attenuation effect to conceal facial redness was achieved.Conclusions: A metronidazole and niacinamide emulgel, also providing cosmetic assistance, was developed using QbD. The emulgel releases metronidazole faster than the creams, but more gradually than the commercially available gel, providing a realistic time frame of drug delivery in accordance with the expected time of residence of the adhesive emulgel over the affected facial area.