Fabrication and characterization of cocoa butter-based caffeine fast-melting tablets.

Aim: The objective of this study was to develop and characterize the physical properties of fast-melting tablets (FMTs) using cocoa butter as the base and caffeine as the model drug. Method: The simple refrigerator freezing method was employed to prepare caffeine-loaded, FMTs from cocoa butter bases. Results: The F3 chosen formulation achieved a disintegration time of 1.20 min ± 0.035, which falls within the specified limit set by the European Pharmacopoeia. The cumulative drug release data of F3, was 88.52 and 94.08% within 60 and 75 min, respectively (NLT 85% as per US FDA requirement). All the other physical test standards for FMTs met the pharmacopeial specifications. Conclusion: Based on the findings, the simple refrigerator freezing method could be used to formulate FMTs.

Patient-friendly natural caffeine-loaded cocoa butter-based fast-melting tablets with rapid disintegration, affordability, safety and biocompatibility are an efficient base for drug delivery.

Physicochemical Characterization of Hydroxyapatite Hybrids with Meloxicam for Dissolution Rate Improvement.

Organic-inorganic hybrids represent a good solution to improve the solubility and dissolution rates of poorly soluble drugs whose number has been increasing in the last few years. One of the most diffused inorganic matrices is hydroxyapatite (HAP), which is a biocompatible and osteoconductive material. However, the understanding of the hybrids' functioning mechanisms is in many cases limited; thus, thorough physicochemical characterizations are needed. In the present paper, we prepared hybrids of pure and Mg-doped hydroxyapatite with meloxicam, a drug pertaining to the Biopharmaceutical Classification System (BCS) class II, i.e., drugs with low solubility and high permeability. The hybrids' formation was demonstrated by FT-IR, which suggested electrostatic interactions between HAP and drug. The substitution of Mg in the HAP structure mainly produced a structural disorder and a reduction in crystallite sizes. The surface area of HAP increased after Mg doping from 82 to 103 m2g-1 as well as the pore volume, justifying the slightly high drug amount adsorbed by the Mg hybrid. Notwithstanding the low drug loading on the hybrids, the solubility, dissolution profiles and wettability markedly improved with respect to the drug alone, particularly for the Mg doped one, which was probably due to the main distribution of the drug on the HAP surface.

Apixaban and clopidogrel in a fixed-dose combination: Formulation and in vitro evaluation.

Fixed-dose combination (FDC) products represent a novel, safe, and cost-effective formulation. Combined use of anticoagulant and antiplatelet medications is common among comorbid cardiovascular patients. This study aimed to formulate FDC tablets for Apixaban and Clopidogrel, as prophylaxis and treatment of thrombo-embolic events. FDC tablets were developed by combining small tablets of Immediate-Release Clopidogrel 75 mg and Extend-Release Apixaban 5 mg through direct compression and wet granulation. Particularly, Apixaban tablets were developed using design expert software, and various types and concentrations of polymers were entered. For Clopidogrel tablets, various diluents were used to develop the formulation. Then, the dissolution profile for each formula was studied. Finally, the optimized formulations were encapsulated within hard gelatin capsules. Apixaban formulation followed zero-order with super case Ⅱ transport mechanism as the dominant mechanism of drug release. The Apixaban drug release rate was affected by the type and concentration of the polymers in the formulation (P < 0.05). As the HPMC concentration was increased, Apixaban release was retarded. For, Clopidogrel, the formulated tablets with spray-dried lactose filler and sodium stearyl fumarate lubricant were found to be stable with good properties. In conclusion, the optimum formulation yielded Clopidogrel and extended-release Apixaban for 24 h with the desired in vitro drug dissolution.

Pharmaceutical Compounding in Veterinary Medicine: Suspension of Itraconazole.

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3-5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and ß-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold.

Comparative Evaluation of Dissolution Performance in a USP 2 Setup and Alternative Stirrers and Vessel Designs: A Systematic Computational Investigation.

The dissolution testing method described in the United States Pharmacopeia (USP) Chapter ⟨711⟩ is widely used for assessing the release of active pharmaceutical ingredients from solid dosage forms. However, extensive use over the years has revealed certain issues, including high experimental intervariability observed in specific formulations and the settling of particles in the dead zone of the vessel. To address these concerns and gain a comprehensive understanding of the hydrodynamic conditions within the USP 2 apparatus, computational fluid dynamic simulations have been employed in this study. The base design employed in this study is the 900 mL USP 2 vessel along with a paddle stirrer at a 50 rpm rotational speed. Additionally, alternative stirrer designs, including the hydrofoil, pitched blade, and Rushton impeller, are investigated. A comparison is also made between a flat-bottom tank and the USP round-bottom vessel of the same volume and diameter. Furthermore, this work examines the impact of various parameters, such as clearance distance (distance between the bottom of the impeller and bottom of the vessel), number of impeller blades, impeller diameter, and impeller attachment angle. The volume-average shear rate (Stv), fluid velocity (Utv), and energy dissipation rates (ϵtv) represent the key properties evaluated in this study. Comparing the USP2 design and systems with the same stirrer but flat-bottom vessel reveals more homogeneous mixing compared to the USP2 design. Analyzing fluid flow streamlines in different designs demonstrates that hydrofoil stirrers generate more suspension or upward movement of fluid compared to paddle stirrers. Therefore, when impellers are of a similar size, hydrofoil designs generate higher fluid velocities in the coning area. Furthermore, the angle of blade attachment to the hub influences the fluid velocity in the coning area in a way that the 60° angle design generates more suspension than the 45° angle design. The findings indicate that the paddle stirrer design leads to a heterogeneous shear rate and velocity distributions within the vessel compared with the other designs, suggesting suboptimal performance. These insights provide valuable guidance for the development of improved in vitro dissolution testing devices, emphasizing the importance of optimized design considerations to minimize hydrodynamic variability, enhance dissolution characterization, and reduce variability in dissolution test results. Ultimately, such advancements hold potential for improving in vitro-in vivo correlations in drug development.

Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation.

Purpose: Isotretinoin (ITN) is a poorly water-soluble drug. The objective of this study was to design a successful liquid self-nanoemulsifying drug delivery system (L-SNEDDS) for ITN to improve its solubility, dissolution rate, and antibacterial activity. Methods: According to solubility and emulsification studies, castor oil, Cremophor EL, and Transcutol HP were selected as system excipients. A pseudo ternary phase diagram was constructed to reveal the self-emulsification area. The developed SNEDDS were visually assessed, and the droplet size was measured. In vitro release studies and stability studies were conducted. The antimicrobial effectiveness against multiple bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and different accessory gene regulator (Agr) variants were investigated for the optimum ITN-loaded SNEDDS formulation. Results: Characterization studies showed emulsion homogeneity and stability (%T 95.40-99.20, A graded) with low droplet sizes (31.87 ± 1.23 nm-115.47 ± 0.36 nm). It was found that the developed ITN-SNEDDS provided significantly a higher release rate (>96 % in 1 h) as compared to the raw drug (<10 % in 1 h). The in vitro antimicrobial activities of pure ITN and ITN-loaded SNEDDS demonstrated a remarkable inhibitory effect on bacterial growth with statistically significant findings (p < 0.0001) for all tested strains when treated with ITN-SNEDDS as compared to the raw drug. Conclusion: These outcomes suggested that SNEDDS could be a potential approach for improving solubility, dissolution rates, and antibacterial activity of ITN.

In vitro Modified Release Studies on Melatoninergic Fluorinated Phenylalkylamides: Circumventing their Lipophilicity for Oral Administration.

INTRODUCTION: In an attempt to circumvent the lipophilicity burden for the oral administration of new potent synthetic melatoninergic fluorine-substituted methoxyphenylalkyl amides, we conducted in vitro modified release studies using carefully selected matrix tablets' biopolymeric materials in different ratios. METHOD: In particular, we sought to attain release profiles of these analogues similar to that of the parent compound, the chronobiotic hormone Melatonin (MLT), and also of the commercially available drug, Circadin®. RESULT: It was found that some of these systems, albeit being more lipophilic than MLT, mimic the in vitro release patterns of melatonin and Circadin®. CONCLUSION: Moreover, a number of these derivatives were proven suitable for dealing with sleep onset problems, whilst others for dealing with combined sleep onset/sleep maintenance dysfunctions.

In Vivo Predictive Dissolution and Biopharmaceutic-Based In Silico Model to Explain Bioequivalence Results of Valsartan, a Biopharmaceutics Classification System Class IV Drug.

The purpose of this study was to predict the in vivo bioequivalence (BE) outcome of valsartan (VALS, BCS class IV) from three oral-fixed combination products with hydrochlorothiazide (HCTZ, BCS class III) (Co-Diovan® Forte as reference and two generic formulations in development) by conducting in vivo predictive dissolution with a gastrointestinal simulator (GIS) and a physiologically based biopharmaceutic model (PBBM). In the first BE study, the HCTZ failed, but the VALS 90% CI of Cmax and the AUC were within the acceptance limits, while, in the second BE study, the HCTZ 90% CI of Cmax and the AUC were within the acceptance limits, but the VALS failed. As both drugs belong to different BCS classes, their limiting factors for absorption are different. On the other hand, the gastrointestinal variables affected by the formulation excipients have a distinct impact on their in vivo exposures. Dissolution tests of the three products were performed in a GIS, and a PBBM was constructed for VALS by incorporating in the mathematical model of the in vitro-in vivo correlation (IVIVC) the gastrointestinal variables affected by the excipients, namely, VALS permeability and GI transit time. VALS permeability in presence of the formulation excipients was characterized using the in situ perfusion method in rats, and the impact of the excipients on the GI transit times was estimated from the HCTZ's in vivo results. The model was able to fit the in vivo BE results with a good prediction error. This study contributes to the field by showing the usefulness of PBBM in establishing in vitro-in vivo relationships incorporating not only dissolution data but also other gastrointestinal critical variables that affect drug exposure in BCS class IV compounds.

Statistical approaches to evaluate in vitro dissolution data against proposed dissolution specifications.

In vitro dissolution testing is a regulatory required critical quality measure for solid dose pharmaceutical drug products. Setting the acceptance criteria to meet compendial criteria is required for a product to be filed and approved for marketing. Statistical approaches for analyzing dissolution data, setting specifications and visualizing results could vary according to product requirements, company's practices, and scientific judgements. This paper provides a general description of the steps taken in the evaluation and setting of in vitro dissolution specifications at release and on stability.

Preparation and Characterization of Theophylline Controlled Release Matrix System Incorporating Poloxamer 407, Stearyl Alcohol, and Hydroxypropyl Methylcellulose: A Novel Formulation and Development Study.

BACKGROUND: Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. METHODS: CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. RESULTS: In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. CONCLUSIONS: The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart.

Hydroxyapatite Nanorods Based Drug Delivery Systems for Bumetanide and Meloxicam, Poorly Water Soluble Active Principles.

Poorly water-soluble drugs represent a challenge for the pharmaceutical industry because it is necessary to find properly tuned and efficient systems for their release. In this framework, organic-inorganic hybrid systems could represent a promising strategy. A largely diffused inorganic host is hydroxyapatite (HAP, Ca10(PO4)6(OH)2), which is easily synthesized with different external forms and can adsorb different kinds of molecules, thereby allowing rapid drug release. Hybrid nanocomposites of HAP nanorods, obtained through hydrothermal synthesis, were prepared with two model pharmaceutical molecules characterized by low and pH-dependent solubility: meloxicam, a non-steroidal anti-inflammatory drug, and bumetanide, a diuretic drug. Both hybrids were physically and chemically characterized through the combined use of X-ray powder diffraction, scanning electron microscopy with energy-dispersive spectroscopy, differential scanning calorimetry, and infrared spectroscopy measurements. Then, their dissolution profiles and hydrophilicity (contact angles) in different media as well as their solubility were determined and compared to the pure drugs. This hybrid system seems particularly suitable as a drug carrier for bumetanide, as it shows higher drug loading and good dissolution profiles, while is less suitable for meloxicam, an acid molecule.

Formulation and characterization of amiodarone-methyl-beta-cyclodextrin inclusion complexes: A molecular modelling perspective.

This study aimed to develop immediate-release tablets containing amiodarone hydrochloride (AM). AM is a BCS class II compound, i.e., high permeable, and poorly soluble. The interactions between amiodarone and methyl-ß-cyclodextrin were DFT-based, theoretically measured, supporting the complexation of AM with cyclodextrin by using methyl-ß-cyclodextrin through a spray-drying process. Thus, increasing substantially the drug solubility to 93.31% and 87.14%, respectively. Solubility studies demonstrated the formation of the Drug-Methyl-ß-cyclodextrin inclusion complex with 1:1 stoichiometry. The complex formation was characterized by SBET, XRD, DSC, SEM, FTIR, and 1H NMR. Complementing, immediate-release tablets containing the inclusion complex were developed by direct compression, and in vitro dissolution studies were performed in gastrointestinal fluids using USP Pharmacopeia standard dissolution rate testing equipment. The dissolution rate of immediate-release tablets was substantially higher than the pristine drug in all mediums evaluated. These results confirm the application of methyl-ß-cyclodextrin as an effective excipient for incorporation in novel dosage forms to increase the solubility of poorly soluble drugs.

Physicochemical reports of gliclazide-carplex solid dispersions and tablets prepared with directly compressible co-processed excipients.

Objectives: The main goal of this research was to develop better tablet formulations by utilizing solid dispersions (SDs) and coprocessing excipients composite to achieve a better release rate of poor water-soluble gliclazide. Methods: The solvent evaporation method made SDs of gliclazide with different carriers carplex 67, carplex 80, and carplex FPS 500 (weight ratio, 1:1). The drug release patterns of the SDs were all evaluated and optimized. The SDs were illustrated by using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Tablet batches FGC-1 to 8 were made using gliclazide-carplex 67 solid dispersions (GC67-SDs) and the co-processed composite of excipients, namely starch-MCC-povidone (SMP) and lactose-MCC-povidone-sodium starch glycolate (LMPS), prepared with coprocessing technology. We evaluated these batches by conducting physicochemical tests and comparing them to the existing commercial brand. Results: In a water medium, the release of gliclazide from SDs peaked within the first 30 min, showing a roughly 5∼6-fold increase compared to plain gliclazide. This quick dissolution rate may be due to the amorphization of the drug, which improved the specific surface area, and increased wettability caused by the hydrophilic properties of carplex particles. This has been confirmed through SEM, DSC, FTIR, and PXRD analysis. All FGC formulations had satisfactory pre-compression factor results, while the post-compression parameters indicated good mechanical strength and homogeneity across the blend. All produced tablets met the weight variation, friability, and disintegration time limit set by the compendia. Through in vitro drug release testing, it was discovered that all FGC tablet batches had consistent and nearly identical release results compared to SDs of gliclazide. However, the FGC-5 to 8 batches containing LMPS composites were determined to be the most effective formulations. In the first 30 min in a water medium, the percentage of drug generated from the FGC-8 tablets involving GC67-SDs and co-processed composite LMPS-4 is approximately 3.5 times higher than the average release of currently marketed products (MPs). After storing the selected FGC tablet batches for three months at 40 °C and 75 % RH, there were no noticeable alterations in the amount of drug and drug release profiles across the batches. Conclusion: Based on these findings, it appears that using the carplex silica-based SDs approach, along with gliclazide and co-processing excipients composite, could result in significant benefits compared to the current commercial brands. This approach could be effectively utilized to create solid dosage forms for drugs that have low solubility in water.

In vitro and in silico methods to investigate the effect of moderately increasing medium viscosity and density on ibuprofen dissolution rate.

Medium viscosity can affect drug dissolution rate, however, it is not usually considered in routine dissolution testing or less complex biorelevant media. The effects of moderately increasing medium viscosity on the in vitro and in silico dissolution of ibuprofen were investigated with two viscosity enhancing agents (VEA) (hydroxypropyl methylcellulose (HPMC) and sucrose), three viscosity levels (range 0.7-5.5 mPa.s), two solubilities and two fluid velocities in the paddle, flow-through and intrinsic dissolution apparatuses. A factorial design analysis highlighted which factors significantly affected key dissolution metrics. Experimental results in the flow-through apparatus (FTA) were compared with in silico dissolution profiles generated by an in-house simulation code (SIMDISSOTM). Increasing viscosity reduced the intrinsic dissolution rate of ibuprofen for both VEAs. The dissolution rate reduction was also observed in the FTA with sucrose, but less so with HPMC, suggesting particle wetting, motion and surface area effects. Particle motion simulations suggested reduced particle lifting times as viscosity increased, indicating an effect of viscosity on particle dispersal. The viscosity- and fluid density-mediated reduction in the dissolution rate observed with sucrose was accurately simulated by SIMDISSOTM, in particular at higher velocities. Velocity had a significant impact on dissolution rates in the paddle apparatus, with a significant viscosity-related reduction in dissolution observed in the low solubility-low velocity scenario. Even small increases in medium viscosity can reduce the dissolution rate of a BCS class II drug, and in silico particle motion and dissolution data can assist interpretation of particulate dissolution behaviour.

Digitalizing the TIM-1 Model Using Computational Approaches─Part Two: Digital TIM-1 Model in GastroPlus.

A TIM-1 model is an in vitro gastrointestinal (GI) simulator considering crucial physiological parameters that will affect the in vivo drug release process. The outcome of these experiments can indicate the critical bioavailability attributes (CBAs) that will impact the fraction absorbed in vivo. The model is widely used in the nonclinical stage of drug product development to assess the bioaccessible fraction of drugs for numerous candidate formulations. In this work, we developed a digital TIM-1 model in the GastroPlus platform. In a first step, we performed validation experiments to assess the luminal concentrations and bioaccessible fractions for two marker compounds. The digital TIM-1 was able to adequately reflect the luminal concentrations and bioaccessible fractions of these markers under different prandial conditions, confirming the appropriate integration of mass transfer in the TIM-1 model. In a second set of experiments, a case example with PF-07059013 was performed, where luminal concentrations and bioaccessible fractions were predicted for 200 and 1000 mg doses under fasted and achlorhydric conditions. Experimental and simulated data pointed out that the achlorhydric effect was more pronounced at the 1000 mg dose, showing a solubility-limited dissolution and, consequently, decreased bioaccessible fraction. Toward future applications, the digital TIM-1 model will be thoroughly applied to explore a link between in vitro and in vivo outcomes based on more case examples with model compounds with the access of TIM-1 and plasma data. Ideally, this digital TIM-1 can be directly used in GastroPlus to explore an in vitro-in vivo correlation (IVIVC) between the fraction dissolved (digital TIM-1 settings) and the fraction absorbed (human PBPK settings).

Digitalizing the TIM-1 Model using Computational Approaches-Part One: TIM-1 Data Explorer.

The TIM-1 gastrointestinal model is one of the most advanced in vitro systems currently available for biorelevant dissolution testing. This technology, the initial version of which was developed nearly 30 years ago and has been subject to a number of significant updates over this period, simulates the dynamic environment of the human gastrointestinal tract, including pH, transfer times, secretion of bile, enzymes, and electrolytes. In the pharmaceutical industry, the TIM-1 system is used to support drug product design and provide a biopredictive assessment of drug product performance. Typically, the bioaccessibility data sets generated by TIM-1 experiments are used to qualitatively compare formulation performance, and the use of bioaccessibility data as inputs for physiologically based pharmacokinetic (PBPK) modeling for quantitative predictions is limited. To expand the utility of the TIM-1 model beyond standard bioaccessibility measurements (which define the fraction available for absorption), we have developed a computational tool, TIM-1 Data Explorer, to describe the fluid and mass balance within the TIM-1 system. The use of this tool allows a detailed inspection and in-depth interpretation of the experimental data. In addition to mass balance calculation, this model also can be used to describe the critical processes a drug substance would undergo during a TIM-1 experiment, such as dissolution, precipitation on transfer from the stomach to duodenum, and redissolution. The TIM-1 Data Explorer was validated in two case studies. In the first case study with paracetamol, we have shown the ability of the simulator to adequately describe mass transfer events within the TIM-1 system, and in the second study with a weakly basic in-house compound, PF-07059013, the TIM-1 Data Explorer was successfully used to describe dissolution and precipitation processes.

The development of a novel simultaneous in vitro dissolution - in situ perfusion system as a potential tool for studying the absorption of solid oral formulation in rat.

The aim of this work is to develop a novel simultaneous in vitro dissolution - in situ perfusion system (SDPS) as a potential tool to evaluate the in vivo performance of solid oral formulation in rat. The innovative nitrendipine (NTD) tablet of Bayotensin mite® made in Germany was used as reference listed drug (RLD), and five generic products from Chinese market were compared with RLD using the in vitro dissolution test method specified by the orange book and the SDPS method developed in this study. Four self-prepared NTD tablets with different proportions of microcrystalline cellulose/starch were employed to investigate the discriminatory ability of the SDPS for formulation. In addition, the predictivity of the SDPS in relation to data from in vivo pharmaceutics studies was evaluated. The 45-min dissolution test and multiple-pH dissolution profiles of generic product 1 and 2 have no difference compared with the RLD, but their dissolution profiles from the SDPS showed statistically significant differences. A biexponential formula successfully described the concentration profiles of self-prepared formulations in SDPS experiments. The kdis (0.08 ± 0.01 ∼ 0.2 ± 0.03 min-1) and ka (about 2.30 × 10-3 min-1) values calculated by the formulas of F1-F3 suggested that the used excipients had no effect on the intestinal absorption of NTD, and it might be the property of active pharmaceutical ingredient that led to the difference among the generics. Furthermore, the in vivo rat pharmacokinetics study results of F1-F3 showed a good correlation (R2 = 0.99) with the SDPS data. In summary, the SDPS is a promising tool to detect the unexpected quality changes of pharmaceutical products in weakly regulated markets, facilitate formulation screening, and potentially reduce animal testing for estimating the in vivo absorption behavior of solid oral formulations. The absorption performance of generic drugs in vivo should be further investigated.

Development and In vitro Evaluation of Aceclofenac Buccal Film.

AIM: This study aimed to formulate and characterize aceclofenac buccal film formulations made of different polymers and evaluate the effects of polymer type on buccal film properties. MATERIALS AND METHODS: Five polymer types, namely hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (SCMC), polyvinyl alcohol (PVA), Eudragit S100, and Eudragit SR100, were used to prepare aceclofenac buccal film formulation either separately or combined by solvent-casting method. These formulations were evaluated in terms of physical appearance, folding test, film weight and thickness, drug content, percentage of elongation, moisture uptake, water vapor permeability, and in vitro drug release. RESULTS: The addition of Eudragit polymer in most of the produced buccal films was unacceptable with low folding endurance. However, the dissolution profile of buccal films made from PVA and Eudragit SR100 provided a controlled drug release profile. CONCLUSION: Buccal films can be formulated using different polymers either individually or in combination to obtain the drug release profile required to achieve a desired treatment goal. Furthermore, the property of the buccal films depends on the type and concentration of the polymer used.

In Vivo Relevance of a Biphasic In Vitro Dissolution Test for the Immediate Release Tablet Formulations of Lamotrigine.

Biphasic in vitro dissolution testing is an attractive approach to reflect on the interplay between drug dissolution and absorption for predicting the bioperformance of drug products. The purpose of this study was to investigate the in vivo relevance of a biphasic dissolution test for the immediate release (IR) formulations of a Biopharmaceutics Classification System (BCS) Class II drug, lamotrigine (LTG). The biphasic dissolution test was performed using USP apparatus II with the dual paddle modification. A level A in vitro-in vivo correlation (IVIVC) was constructed between the in vitro partition into the octanol and absorption data of the reference product. A good relation between in vitro data and absorption was obtained (r2 = 0.881). The one-compartment open model was introduced to predict the human plasma profiles of the test product. The generic product was found to be bioequivalent to the original product in terms of 80-125% bioequivalence (BE) criteria (85.9-107% for the area under the plasma concentration curve (AUC) and 82.7-97.6% for the peak plasma concentration (Cmax) with a 90% confidence interval (CI)). Overall, it was revealed that the biphasic dissolution test offers a promising ability to estimate the in vivo performance of IR formulations of LTG, providing considerable time and cost savings in the development of generic drug products.

Application of a Customised Franz-Type Cell Coupled with HPTLC to Monitor the Timed Release of Bioactive Components in Complex Honey Matrices.

The aim of this study was to assess the release profile of components in five different honeys (a New Zealand Manuka and two Western Australian honeys, a Jarrah honey and a Coastal Peppermint honey) and their corresponding honey-loaded gel formulations using a custom-designed Franz-type diffusion cell in combination with High-Performance Thin-Layer Chromatography (HPTLC). To validate the suitability of the customised setup, release data using this new approach were compared with data obtained using a commercial Franz cell apparatus, which is an established analytical tool to monitor the release of active ingredients from topical semisolid products. The release profiles of active compounds from pure honey and honey-loaded formulations were found to be comparable in both types of Franz cells. For example, when released either from pure honey or its corresponding pre-gel formulation, the percentage release of two Jarrah honey constituents, represented by distinct bands at RF 0.21 and 0.53 and as analysed by HPTLC, was not significantly different (p = 0.9986) at 12 h with over 99% of these honey constituents being released in both apparatus. Compared to the commercial Franz diffusion cell, the customised Franz cell offers several advantages, including easy and convenient sample application, the requirement of only small sample quantities, a large diffusion surface area, an ability to analyse 20 samples in a single experiment, and lower cost compared to purchasing a commercial Franz cell. Thus, the newly developed approach coupled with HPTLC is conducive to monitor the release profile of minor honey constituents from pure honeys and honey-loaded semisolid formulations and might also be applicable to other complex natural-product-based products.