Kollicoat IR Research Articles

Dosage by design – 3D printing individualized cabozantinib tablets with immediate release

Production of patient-specific dosage forms is important to improve patient adherence and effectiveness while reducing the prevalence and severity of adverse effects. Due to its possibility of rapid prototyping 3D printing can be used to produce individual dosages while utilizing techniques such as hot melt extrusion to increase the bioavailability of poorly soluble drugs. In this work, Parteck MXP and Kollicoat IR were used as water-soluble polymer bases for formulation development for 3D printing of various dosages incorporating cabozantinib while enabling immediate release. The effect of tablet design and the excipients sorbitol, croscarmellose sodium, and sodium starch glycolate was investigated for this goal. A way to calculate the size of tablets for predetermined dosages is proposed to enable the printing of individual strengths from one formulation. Rheological data were collected to deepen the understanding of the role of melt viscosity in 3D printing and hot melt extrusion processes. The production of immediate-release cabozantinib tablets containing every therapeutically relevant dosage in a single unit produced by two-step 3D printing was realized.

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

Development of multiple structured extended release tablets via hot melt extrusion and dual-nozzle fused deposition modeling 3D printing

The study aims to fabricate extended release (ER) tablets using a dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing technology based on hot melt extrusion (HME), using caffeine as the model compound. Three different ER tablets were developed, which obtained “delayed-release”, “rapid-sustained release”, and “release-lag-release” properties. Each type of tablet was printed with two different formulations. A novel printing method was employed in this study, which is to push the HME filament from behind with polylactic acid (PLA) to prevent sample damage by gears during the printing process. Powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC) results showed that caffeine was predominately amorphous in the final tablets. The dissolution of 3D printed tablets was assessed using a USP-II dissolution apparatus. ER tablets containing PVA dissolved faster than those developed with Kollicoat IR. Overall, this study revealed that ER tablets were successfully manufactured through HME paired with dual-nozzle FDM 3D printing and demonstrated the power of 3D printing in developing multi-layer tablets with complex structures.

Formulation, Optimization, and Evaluation of Gliclazide loaded Nanosuspension for Dissolution Rate Enhancement

Diabetes mellitus is a prolonged metabolic condition categorized through elevated blood glucose levels. To treat this condition, oral antihyperglycemic medications like gliclazide, a second-generation sulfonylurea insulin secretagogue, are commonly used. Gliclazide comes into the biopharmaceutical classification system (BCS) class-II types, known for its lower solubility. To enhance its solubility, gliclazide was integrated into nanosuspensions. This study focused on formulating these gliclazide nanosuspensions using Kollicoat IR and Soluplus through the anti-solvent-precipitation method, through optimization achieved using the Box Behnken Design. Key parameters assessed included particle size (224 ± 1.23 nm) and entrapment efficiency (95.65 ± 0.12%). The drug release studies conducted on pH 7.4 indicated that over 95% of the drug was released within 30 minutes for the nanosuspension, whereas the pure drug solution released less than 70% in the same time frame, indicating immediate release with the nanosuspension. The morphology was examined using scanning electron microscopy (SEM), while fourier transform infrared (FTIR), X-Ray diffractometers (XRD), and differential scanning calorimeter (DSC) analyses confirmed the presence of the drug within the nanosuspension. In summary, the incorporation of gliclazide into nanosuspensions proved successful, resulting in enhanced release characteristics and ameliorated solubility.

Development, Optimization and Characterization of Glimepiride Nanosuspension with Improved Solubility and Dissolution

Current work describes the development of nanoparticulate suspension (NPs) of glimeperide (GLMP) with enhanced solubility and bioavailability. Using the ultrasonication-assisted precipitation method, GLMP-NP was developed and optimized through the use of a three-factor two-level full factorial design methodology. Drug release, size of a particle, and encapsulation efficiency from nanoparticles were considered as dependent variables while the concentration of Hydroxy propyl cellulose (HPC SSL), Kollicoat IR, and sonication time were considered as independent variables. According to the study, every independent variable significantly affected the dependent variables (p <0.05). The size of the particle GLMP-NP ranged between 159 (F2) to 505 nm (F8) while EE varied from 32 (F8) to 75% (F2). The DR of the GLMP-NP observed at 10 min ranged between 35 (F8) to 100% (F2). A significant enhancement in dissolution rate was observed in GLMP-NPs (F1-F8) in comparison to pure GLMP. It was discovered that pure GLMP dissolved in 27.25 ± 6.8 μg/mL of double-distilled water, while GLMP-NP exhibited 3.50 to 6.58-fold enhancement in saturation solubility. FTIR and DSC analysis revealed excellent compatibility between GLMP and excipients. XRD study confirmed the amorphous nature of the nanoparticles while SEM analysis revealed a smooth surface. In conclusion, this study demonstrates the substantial improvement in dissolution rate and solubility of pure GLMP when formulated as nanoparticles.

Improvement of in vitro dissolution profile of poorly aqueous soluble anti-parasitic agent ivermectin using novel hydrophilic polymeric carriers

Ivermectin (IVM), a BCS Class II drug with weak water solubility, has minimal oral absorption and dissolution. This study aims to enhance the dissolution profile of IVM by performing solid dispersion methods using four hydrophilic polymers: Kollicoat IR, Kollidon 90F, poloxamer 407, and hydroxypropyl methylcellulose (HPMC). The solid dispersion formulations (SDF) were made through physical mixing, solvent evaporation, and melt solvent/fusion. Using three ratios of IVM and hydrophilic carriers (1:1, 1:2, and 1:3), the cumulative release rate of IVM from formulations formed by physical mixing, solvent evaporation, and fusing was much larger than pure IVM (10%). IVM release rates from formulations including Poloxamer 407, Kollicoat IR, and HPMC polymers were 76% (fusion technique), 69% (physical mixing), and 47% (solvent evaporation method). The research demonstrated that fusion optimized drug solubility better than physical mixing and solvent evaporation. The research found that SD of weakly water-soluble IVM with Kollicoat IR/Poloxamer 407 improves its in vitro dissolving profile much better. Bangladesh J. Sci. Ind. Res. 58(4), 209-220, 2023

Comparison of Two Grafted Copolymers, Soluplus and Kollicoat IR, as Solid Dispersion Carriers of Arteether for Oral Delivery Prepared by Different Solvent-Based Methods

Comparison of Two Grafted Copolymers, Soluplus and Kollicoat IR, as Solid Dispersion Carriers of Arteether for Oral Delivery Prepared by Different Solvent-Based Methods

Hot Melt Extrusion for Improving the Physicochemical Properties of Polydatin Derived from Polygoni cuspidati Extract; A Solution Recommended for Buccal Applications.

Three different types of solid dispersions based on polyvinyl polymers and related copolymers (Kollidon® VA64, Soluplus® and Kollicoat IR®) comprising polydatin-rich Polygoni cuspidati extract were prepared by hot melt extrusion. The systems were characterized using X-ray powder diffraction, infrared spectroscopy as well as by polydatin release and in vitro permeability. Mucoadhesive tablets were prepared from the extrudates based on Kollidon® VA64 and Soluplus® to obtain a suitable pharmaceutical form, where (hydroxypropyl)methyl cellulose was added as a mucoadhesive agent. The tablets were evaluated in terms of the kinetics of polydatin release as well as their mucoadhesive properties. The best tabletability properties, polydatin release profile and adequate mucoadhesive properties were obtained by the formulation containing the Kollidon® VA64-based extrudate, which makes it an excellent prototype for enhancing the release of poorly water-soluble compounds.

Hot Melt Extruded Posaconazole-Based Amorphous Solid Dispersions-The Effect of Different Types of Polymers.

Four model polymers, representing (i) amorphous homopolymers (Kollidon K30, K30), (ii) amorphous heteropolymers (Kollidon VA64, KVA), (iii) semi-crystalline homopolymers (Parteck MXP, PXP), and (iv) semi-crystalline heteropolymers (Kollicoat IR, KIR), were examined for their effectiveness in creating posaconazole-based amorphous solid dispersions (ASDs). Posaconazole (POS) is a triazole antifungal drug that has activity against Candida and Aspergillus species, belonging to class II of the biopharmaceutics classification system (BCS). This means that this active pharmaceutical ingredient (API) is characterized by solubility-limited bioavailability. Thus, one of the aims of its formulation as an ASD was to improve its aqueous solubility. Investigations were performed into how polymers affected the following characteristics: melting point depression of the API, miscibility and homogeneity with POS, improvement of the amorphous API's physical stability, melt viscosity (and associated with it, drug loading), extrudability, API content in the extrudate, long term physical stability of the amorphous POS in the binary drug-polymer system (in the form of the extrudate), solubility, and dissolution rate of hot melt extrusion (HME) systems. The obtained results led us to conclude that the physical stability of the POS-based system increases with the increasing amorphousness of the employed excipient. Copolymers, compared to homopolymers, display greater homogeneity of the investigated composition. However, the enhancement in aqueous solubility was significantly higher after utilizing the homopolymeric, compared to the copolymeric, excipients. Considering all of the investigated parameters, the most effective additive in the formation of a POS-based ASD is an amorphous homopolymer-K30.

An evaluation of film coating materials and their predicted oro-esophageal gliding performance for solid oral dosage forms

Oral drug therapy is generally provided in the form of solid oral dosage forms (SODF) that have to be swallowed intact and move throughout the oro-esophageal system until reaching the stomach. Previous studies have provided evidence that the surface characteristics of SODF play an important role during oro-esophageal transit, while their nature may govern the degree of interaction (adhesiveness) with the esophageal tissue. In order to better predict the synergy of SODF surface coatings to the esophageal mucosa during drug administration therapy, an in vitro system has been implemented to investigate their gliding performance across an artificial mucous layer. Coating formulations comprised of different film-forming and slippery-inducing agents were evaluated using the established in vitro artificial mucous system. Polyvinyl alcohol (PVA), polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC) and Kollicoat IR (K-IR) were applied as film-forming agents, whereas sodium alginate (SA), carrageenan (CA) and gellan gum (GG) were evaluated both as film-forming and slippery-inducing agents. Carnauba wax (CW), lecithin (LE), xanthan gum (XG) and sodium lauryl sulfate (SLS) were applied as slippery-inducing agents. Two polar wax coating materials were also investigated for their gliding performance. GG displayed suitable gliding performance when applied as film-forming agent, being this effect enhanced when combined with CW/SLS and XG, as slippery-inducing agents. Optimal performance was also demonstrated by the polar waxes. The multivariate approach applied allowed a higher granularity in the analysis of the gliding results and supported a better identification of combinations of excipients and respective concentrations required for improved gliding performance, as such, the obtained gliding results support the identification of coating materials and their suitable combinations that are predicted to improve in vivo swallowing safety.

Development of ibuprofen tablet with polyethylene oxide using fused deposition modeling 3D-printing coupled with hot-melt extrusion

Ibuprofen is known to plasticize several polymers used in hot-melt extrusion, and it is considered challenging to achieve immediate release for ibuprofen using fused deposition modeling. Therefore, this study aimed to print ibuprofen tablets with a focus on achieving rapid release. Polyethylene oxide (Polyox WSR N80) was used as the main matrix to form the ibuprofen filament, because of its water-soluble properties and ability to manifest suitable mechanical properties, even with high drug loading (40% w/w). Several release modifiers, such as Kollidon VA64, Kollidon 12PF, Kollicoat IR, Kollidon CL, and mannitol, were added separately to the formulation, following which their effects on enhancing the drug release rate were investigated. Their effects on the mechanical properties of the filaments have also been assessed in this study. It was demonstrated that adding soluble Kollidon grades, such as Kollidon VA64 and Kollidon 12PF, enhanced the drug release rate. In addition, the tablet design with a high surface-to-mass ratio was beneficial for increasing the drug release rate. However, incorporation of the release modifiers discussed above decreased the flexural modulus of the filament. Additionally, it is important to tailor the printing parameters by considering the properties of the filament, to acquire good quality printlets. The tablet consisting of 30% ibuprofen and 20% Kollidon VA64 at the highest dose used in this study (84 mg) released 80% of the drug, in approximately 90 min. To further increase the release rate and drug dose, other additives, such as viscosity-increasing agents and reinforcing additives, can be explored. This study shows the potential of fabricating ibuprofen tablets with rapid release characteristics using Polyox WSR N80, via fused deposition modeling 3D-printing.

Evaluation of in vitro Dissolution Profile and Physicochemical Characterization of Polymer Based Formulations of Sparingly Soluble Rosuvastatin

Rosuvastatin (RVT) is a BCS class II antilipidemic crystalline drug, which exhibits low bioavailability due to its very poor aqueous solubility; therefore, it is challenging to develop a proper formulation of RVT. To enhance solubility and bioavailability of this API, an attempt has been made by implementing solid dispersion technique. Solid dispersion (SD) technique is a solubility enhancing technique where one or more active entities are dispersed in an inert medium (matrix or carrier) at solid state. In this study, different ratios of Kollicoat® IR (KIR) and Kollidon® 90F (KF90) polymers were used with API to prepare various formulations by physical mixing (PM) and SD approaches; here solvent evaporation technique was used whereas methanol was used as solvent which was completely evaporated from the homogenously dispersed system by placing in a water-bath at 60-65°C and then in oven for 30 minutes at 50 °C. Among the formulations, RVT-KF90 SD formulations showed the most promising result in in-vitro study in terms of drug release profile (78.04 – 99.21%) in comparison to pure RVT (63.1%) and physical mixing of RVT with those polymers. USP dissolution apparatus type II was used at 37°C ± 0.5°C with 50 rpm to conduct the in-vitro experiment. The experiment also unraveled that the dissolution of RVT improved with increasing the amounts of polymers. Subsequently, stability of the developed formulations was conducted by Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) as well as scanning electron microscopy (SEM). The results obtained from FTIR ensured no involvement of any significant drug-excipient interaction. Moreover, the DSC study signified thermal stability at high temperature. Besides, the SEM micrograph illustrated homogenous distribution of RVT in the polymer and transformation of crystal-like RVT into amorphous formulations. Dhaka Univ. J. Pharm. Sci. 20(2): 199-211, 2021 (December)

Theoretical and experimental validation of praziquantel with different polymers for selection of an appropriate matrix for hot-melt extrusion

The selection of an appropriate matrix for the preparation of amorphous extrudate in hot-melt extrusion (HME) deals with the study of various solid-state properties of drugs and polymers. Therefore, it is necessary to have an appropriate knowledge of drug-polymer miscibility, the interaction between the drug-polymer on mixing, and Gibb's free thermal energy of mixing to screen polymers through thermodynamic phase diagrams, to be suitable amorphous matrix system for HME. Here, we evaluated the possibility of three different polymers, namely, Eudragit®EPO, polyvinyl alcohol (PVA), Kollicoat®IR (KIR) with Praziquantel (PZQ), with proper validation of the Flory-Huggins theory and construction of the phase diagram using the melting point depression approach to determine a suitable matrix for HME. The solubility parameter theoretical calculation approach was used as a preliminary study to validate the miscibility of PZQ with three different polymers. Theoretical and experimental validation studies using the Flory-Huggins interaction parameter value using the melting point depression approach and the effect of PZQ loading on the interaction parameter were systematically validated to predict thermodynamic phase diagrams and Gibbs free energy of mixing for screening these polymers for the preparation of amorphous extrudate. Using the phase diagram, the thermal processing temperature for the HME was determined using a T-φ phase diagram to obtain an appropriate matrix. The obtained extrudates were further validated through physical appearance, microscopic structure, thermal and functional group characterizations, followed by the PZQ assay. Thus, considering the solid-state properties, the processing parameters of HME were selected to obtain stable extrudates and an appropriate matrix for PZQ loading.

Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation

The goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F 127), Kollicoat IR (KL), hydroxypropyl methylcellulose E3 (HPMC), xanthan gum (XG), polyvinyl pyrrolidone K30 (PVP), and sodium lauryl sulfate (SLS) upon the resulting nanoparticles was investigated. Additionally, the ex vivo release of the FLZ nanonized particles from ophthalmic gel bases was studied by using goat cornea, and the ocular pharmacokinetics of appropriate ophthalmic gel base containing optimized drug nanoparticle formula compared to the untreated drug were studied in rabbits. FLZ nanoparticles were successfully prepared with different concentrations of stabilizers. However, the effects of these stabilizers on nanoparticle size and zeta potential values varied according to the concentration and type of stabilizer used. Based on differential scanning calorimetry, the drug was in its amorphous state in the tested nanoparticle formulations. The results of ex vivo ocular diffusion of the FLZ nanoparticle gel formulations revealed an improvement compared to that with the FLZ untreated gel. Nanoparticle formula (F3) prepared by using 5% PL F127 showed small particle size (352 ± 6.1 nm) with zeta potential value of −18.3 mV with highest ex vivo release rate from goat cornea (100% after 6 h). Moreover, the AUC0-8h from ocular application of FLZ from sodium alginate gel containing nanoparticle formula F3 was 1.4-fold higher than that after its administration in the untreated formula. Based on our findings, the ophthalmic gel formulations containing FLZ nanoparticles enhanced drug corneal permeation and improved the ocular pharmacokinetic parameters.

A straw for paediatrics: How to administer highly dosed, bitter tasting paracetamol granules

Paediatric practice requires various dosing forms that are acceptable for children of different ages and abilities. A straw prefilled with a drug formulation might serve as a dosing form, especially for children and patients with swallowing difficulties. Using a two-step procedure, we developed granulated coated particles of bitter tasting paracetamol that are appropriate for use in a newly developed straw with two valves to assure liquid flow towards the oral cavity. The paracetamol crystals were coated with five different polymers (water-soluble, entero-soluble) to assure the duration of the taste-masking properties for several minutes during sipping of the drug. As none of these polymer coats assured small enough liquid volumes needed to empty the straw (20 mL) or low enough vacuum for easy drug consumption (130 mbar), the coated crystals were granulated with trehalose-erythritol powder mixture. Acceptable results were obtained with these granulated coated paracetamol particles when polyvinyl alcohol/polyethylene glycol graft copolymer (Kollicoat IR) or a mixture of this polymer with polyvinyl alcohol (Kollicoat Protect) were used. Dissolution tests in water and acidic media confirmed the taste-masking functionality of these particles during drinking simulation and immediate release of paracetamol in the stomach (85% in <30 min at pH 1.2, 4.5).

Improving the drug dissolution profile of poorly aqueous soluble lovastatin using hydrophilic polymers by solid dispersion and physical mixing techniques

Background: Improvement of the dissolution rate and solubility of poorly aqueous soluble drugs using solid dispersion (SD) techniques are considered as one of the most attractive processes. The focus of the current research project is to investigate the dissolution property of lovastatin (LVT) using SD technology comprising of drug, excipients, and carrier. Aim and Objectives: The main objective of this study is to augment the dissolution profile of LVT, a statin medication belongs to biopharmaceutics classification system Class II drugs and water-insoluble, by applying SD procedures. Materials and Methods: The melt solvent/fusion and physical mixing (PM) methods were employed to prepare the SDs. PMs of LVT and hydrophilic carriers such as Kollidon 90F and Kollicoat IR were prepared and investigated at three different ratios (1:0.5, 1:1, and 1:2). SD formulation of LVT was prepared by melt solvent or fusion technique using hydrophilic carriers and polyethylene glycol at 1:0.5:5, 1:1:5, and 1:2:5 ratios. The characterization of the prepared SD formulations was investigated by scanning electron microscopy (SEM) and in vitro dissolution studies. Results: Physical characterization experiment showed that SD of LVT prepared by fusion technique demonstrated improved dissolution property compared to the PM formulations or pure drug attributable to the conversion of LVT into an amorphous and/or less crystalline form. The results of in vitro dissolution enhancement order followed the same trend both in SD formulations and in PMs (Kollicoat IR> Kollidon 90F). The SEM analyses indicated that crystallinity of drug decreased in the SD formulation suggesting a portion of LVT could be in an amorphous state. Conclusion: The outcomes suggested a remarkably increased dissolution rate of LVT through SD systems prepared with suitable and correct proportion of polymers by melt solvent method and PM technique when compared with the pure drug dissolution profile. This was because of the hydrophilic carriers which affected the crystal structure of the drug. Hence, this approach of SD technique utilizing the above-mentioned carriers could be employed as a substantial formulation strategy to enhance the in vitro dissolution rate which, in turn, may improve the oral bioavailability of the water-insoluble drugs.

Preparation and dissolution characteristic evaluation of carvedilol-Kollicoat IR solid dispersions with HPMC and MC as combined carriers

In this study, the abilities of hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC) as nonionic surfactants to improve the dissolution rate of carvedilol solid dispersions (CAR SDs) with Kollicoat IR as a carrier were clearly demonstrated. CAR SDs were prepared using the solvent evaporation method, and their physicochemical properties were characterized by scanning electron microscopy (SEM) and Powder X-Ray diffraction (PXRD). The results suggested that CAR in SDs existed in an amorphous form. In vitro dissolution experiments and molecular docking (MD) simulations were conducted to confirm the storage stability of CAR SDs. In order to study the mechanism of solubilization ability, molar solubilization ratio (MSR) and micelle-water partition coefficient (Kmic) were calculated. The results showed that the MSR and lg Kmic values of MC/Kollicoat IR 1:3 were around 30 fold higher than the single surfactant. Above all, HPMC and MC have great potentials to improve the dissolution characteristics of CAR-Kollicoat IR SDs.

FORMULATION OPTIMIZATION AND EVALUATION OF MOUTH DISSOLVING FILM OF APREPITANT

Objectives: The aim of the present research is to prepare mouth dissolving film of aprepitant used in the prevention and treatment of post-operative nausea and vomiting.&#x0D; Methods: The MDF was prepared using Kollicoat IR, PEG 400, and spraying technique. Formulation was optimized by central composite design. Compatibility study was carried out using Fourier-transform infrared and differential scanning calorimetry. The films were evaluated for thickness, folding endurance, weight variation, disintegration time, dissolution studies, drug content, and in vitro diffusion test.&#x0D; Results: From the results, it was found that there was no drug excipient interaction. The prepared optimized batch AP2 showed disintegration time 18 sec, highest dissolution rate 101.53%, drug diffused 39.58 mg/cm2 within 10 min and also passes all the physicochemical parameters. It was concluded that plasticizer PEG 400 plays a very much important role in the preparation of aprepitant MDF.&#x0D; Conclusion: MDF of aprepitant was found to be a better option in the prevention and treatment of post-operative nausea and vomiting by the way of fast onset of action for patient convenience and compliance. In the near future, the MDF market will expand very fastly to treat various diseases.

Fabrication of Dissolvable Microneedle Patches Using an Innovative Laser-Cut Mould Design to Shortlist Potentially Transungual Delivery Systems: In Vitro Evaluation.

There has been a great interest towards transungual delivery systems due to limited drug penetration for the treatment of nail diseases. More important, antifungal oral medicaments used may cause serious side effects including liver damage. Therefore, we propose non-oral dissolvable microneedle (MN) patch to strike the poor permeability of the nail. We report the design of MN patch mould using a laser-cutting machine and solvent casting of several hydrophilic polymers to fabricate these MN patches. Formulations were evaluated for their in vitro release and penetration properties and selected based on physical characterization for compatibility (differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD)), dimension repeatability and drug content uniformity. A 72-array of cone-shaped MN patch mould was successfully constructed on polymethylmethacrylate sheets. Interval and frequency of laser exposure were pivotal to determine the needle sharpness, attained unexpectedly at a low level of circa 30μm. F1 platform of polyvinyl alcohol, kollicoat IR®, ethylene glycol and gelatin showed circa 74% penetration of methylhydroxy-4-benzoate (F1(A)) over 24h, whereas F2 (same as F1-A with the addition of poloxamer 338) resulted in an almost 42% of this drug retention in the bovine hoof (24h). Both formulations are likely to be useful for onychomycosis treatment. F1 polymers also afford enhanced permeability (almost 73.5% after 24h) of terbinafine hydrochloride into the hoof (F1(B)). However, F3 (chitosan, gelatin and ethylene glycol) presents the prospect of developing MN patch for this drug with almost complete hoof penetration (circa 96.3% after 24h). All medicated formulations have shown similar mechanical properties after ageing for 1year under dry conditions.

Physicochemical and pharmacodynamic evaluation of pioglitazone binary systems with hydrophilic carriers

Pioglitazone (PGZ) is an antidiabetic agent belongs to thiazolidinediones. Binary systems of PGZ in the matrices of kollicoat IR (KL) and gelucire (GL) at different weight ratios were prepared by kneading and co-evaporation methods, respectively. The drug solid dispersions were characterized in terms of in vitro dissolution studies, differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). The effects of PGZ-KL (1:4) solid dispersion on the body weight, blood glucose, renal and hepatic functions of the diabetic rats were evaluated. Enhanced drug dissolution was observed in the case of PGZ-KL binary systems depending on the drug to polymer weight ratio. A reduction of 39.7, 32.7 and 26.6% for diabetic control, PGZ untreated and PGZ-KL (1:4), respectively, was recorded after 2 weeks. PGZ-KL (1:4) solid dispersion also showed significantly lower glucose blood level (p < 0.05) compared to the diabetic control group along the period of experiment. The level of ALT was highly significantly decreased in the animal group treated with PGZ-KL solid dispersion (p < 0.001). However, treatment of diabetic rats with either PGZ-KL or PGZ untreated significantly reduced the level of creatinine compared to the diabetic control and the difference between them was non-significant.