Development of Orodispersible Tablets with Solid Dispersions of Fenofibrate and Co-Processed Mesoporous Silica for Improved Dissolution.

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption.

The comparison of melt technologies based on mesoporous carriers for improved carvedilol dissolution.

High-shear (HS) melt granulation and hot melt extrusion (HME) were compared as perspective melt-based technologies for preparation of amorphous solid dispersions (ASDs). ASDs were prepared using mesoporous carriers (Syloid 244FP or Neusilin US2), which were loaded with carvedilol dispersed in polymeric matrix (polyethylene glycol 6000 or Soluplus). Formulations with high carvedilol content were obtained either by HME (11 extrudates with polymer:carrier ratio 1:1) or HS granulation (6 granulates with polymer:carrier ratio 3:1).

Taste-masking methods in multiparticulate dosage forms with a focus on poorly soluble drugs.

In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms.

Investigating the Influence of Processing Conditions on Dissolution and Physical Stability of Solid Dispersions with Fenofibrate and Mesoporous Silica.

The study aimed to enhance the solubility of the poorly water-soluble drug, fenofibrate, by loading it onto mesoporous silica, forming amorphous solid dispersions. Solid dispersions with 30% fenofibrate were prepared using the solvent evaporation method with three solvents (ethyl acetate, acetone, and isopropanol) at different temperatures (40 °C, boiling point temperature). Various characteristics, including solid-state properties, particle morphology, and drug release, were evaluated by different methods and compared to a pure drug and a physical mixture of fenofibrate and silica.

Evaluation of Monolayer and Bilayer Buccal Films Containing Metoclopramide.

The objective of this study was to develop buccal film formulations containing metoclopramide hydrochloride monohydrate (MCP) with and without a backing layer and to evaluate their release properties and physiochemical stability. The crystallization of MCP in the polymer matrix was monitored with image analysis techniques for rapid and scalable observation. The results showed that the addition of a protective layer and its thickness significantly affected the release rate and crystallization behavior of MCP in the formulations.

Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study.

Recently, nanocrystal dispersions have been considered as a promising formulation strategy to improve the bioavailability of the deuterated pyrazoloquinolinone ligand DK-I-56-1 (7‑methoxy-2-(4‑methoxy-d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one). In the current study, the freeze-drying process (formulation and process parameters) was investigated to improve the storage stability of the previously developed formulation. Different combinations of lyoprotectant (sucrose or trehalose) and bulking agent (mannitol) were varied while formulations were freeze-dried under two conditions (primary drying at -10 or -45 °C).

Effect of process parameters in high shear granulation on characteristics of a novel co-processed mesoporous silica material.

In this study, insights into the development and optimization of a co-processed excipient based on mesoporous silica are presented. The main advantage of such a material is that it is appropriate for direct tablet compression and has a sufficiently large specific surface area to be suitable for potential subsequent drug loading and formulation of (amorphous) solid dispersions. Our aim was to use a Design of Experiments approach to investigate which process parameters in high shear granulation affect the characteristics of such a co-processed material.

Formulation and Characterization of Buccal Films Containing Valsartan with Additional Support from Image Analysis.

The present study was aimed to the development and characterization of valsartan-containing buccal films with an introduction to a novel technique of image analysis. Visual inspection of the film provided a wealth of information that was difficult to quantify objectively. The obtained images of the films observed under the microscope were embedded in a convolutional neural network (CNN).

Spherical Agglomerates of Lactose Reduce Segregation in Powder Blends and Improve Uniformity of Tablet Content at High Drug Loads.

We report here on improved uniformity of blends of micronised active pharmaceutical ingredients (APIs) using addition of spherical agglomerates of lactose and enhanced blend flow to improve tablet content uniformity with higher API loads. Micromeritic properties and intra-particle porosity (using nano-computed X-ray tomography) of recently introduced spherical agglomerates of lactose and two standard lactose grades for the direct compression processes were compared. Powder blends of the individual lactose types and different micronised API drug loads were prepared and subjected to specific conditions that can induce API segregation.

Application of commercially available mesoporous silica for drug dissolution enhancement in oral drug delivery.

Due to the high number of poorly water-soluble active pharmaceutical ingredients, oral drug delivery development has become challenging. One of the strategies to enhance drug solubility and to achieve high oral bioavailability is to formulate such compounds into amorphous solid dispersions. In recent years, porous materials have been investigated as possible carriers into which a drug can be adsorbed, such as mesoporous silica, in particular.

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.

Spherical agglomerates of lactose as potential carriers for inhalation.

We report here on spherical lactose agglomerates as potential carriers for inhalation applications. Micromeritic properties of three spherical lactose agglomerates (SA-A, SA-B, SA-C) and a standard lactose inhalation grade carrier (Lactohale 100; LH100) were evaluated and compared. Ordered mixtures with micronized salbutamol sulfate as the model active pharmaceutical ingredient (API) and lactose carriers at two drug loadings (2 wt%, 5 wt%) were prepared, and in-vitro aerosolization performance was assessed.

Design of Experiments for Optimization of the Lactose Spherical Crystallization Process.

This study provides a comprehensive assessment of the parameters of the spherical crystallization process and their impact on the micromeritic properties of lactose spherical agglomerates. A recently introduced definitive screening design was used to study various process parameters, with particular focus on building predictive models. The parameters included were: lactose solution concentration; volume ratio between the antisolvent and the whole crystallization system; crystallization system temperature; velocity of the addition of the lactose water solution; agitation velocity; and agitation time after whole addition of the lactose solution.

Advanced flow cell design for in vitro release testing of mucoadhesive buccal films.

Films for buccal application are a slowly emerging new platform for drug delivery. There remains a lack of analytical techniques for the determination of in vitro active pharmaceutical ingredient release. The aim here was to develop an alternative method to the commonly used United States Pharmacopoeia (USP) 2 method, based on the flow-through cell.

Excipients in freeze-dried biopharmaceuticals: Contributions toward formulation stability and lyophilisation cycle optimisation.

Biopharmaceuticals are one of the fastest growing areas within the pharmaceutical industry. As protein drugs require parenteral administration, they are commonly formulated as aqueous solutions. However, this is not always feasible due to their general instability.

Elucidating molecular properties of kappa-carrageenan as critical material attributes contributing to drug dissolution from pellets with a multivariate approach.

Multivariate data analysis (MVDA) and artificial neural networks (ANN) are supporting statistical methodologies required for successful development and manufacturing of drug products. To address this purpose, a complex dataset from 49 industrially produced capsules filled with pellets was first analyzed through the development of a multiple linear regression model focused on determining raw material attributes or process parameters with a significant impact on drug dissolution. Based on the model, the following molecular and micrometrics properties of κ-carrageenan have been identified as critical material attributes with the highest contribution to drug dissolution: molecular weight and polydispersity index, viscosity, content of potassium ions, wettability, particle size, and density.

The formation and effect of mannitol hemihydrate on the stability of monoclonal antibody in the lyophilized state.

Crystalline bulking agent in lyophilized biopharmaceutical formulations provides an elegant lyophilized cake structure and allows aggressive primary drying conditions. The interplay between amorphous and crystalline state of excipients heavily influence the stability of lyophilized biological products and should be carefully evaluated in the formulation and process development phase. This study focuses on: (1) elucidating the influence of formulation and lyophilization process variables on the formation of different states of mannitol and (2) its impact on model monoclonal antibody stability when compared to sucrose.

Matrix Tablets for Controlled Release of Drugs Incorporated Using Capillary Absorption.

Cost and time effectiveness make direct tableting still the favored method for tablet production. Among its most noticeable limitations in application is the non-uniformity (and/or inhomogeneities) in the contents of the resulting tablets, possibly leading to inconsistencies in required tablet properties. The efficiency of direct tableting is mostly affected by surface properties of the components to be tableted, which govern the final tablet mechanical and chemical properties and can influence the liquid capillary rise that the tablets exhibit after ingestion.

Modified equation for particle bonding area and strength with inclusion of powder fragmentation propensity.

The paper considers a novel, modified equation for evaluation of relationship between tablet tensile strength, bonding area and bonding strength with inclusion of fragmentation as particle deformation mechanism. Four types of lactose particles for direct compression were assessed for their micromeritic and mechanical properties (compressibility and compactibility), with particular focus on fragmentation behaviour, bonding area and bonding strength. Compressibility properties were assessed using three established models.

Novel Budesonide Particles for Dry Powder Inhalation Prepared Using a Microfluidic Reactor Coupled With Ultrasonic Spray Freeze Drying.

Budesonide (BDS) is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers, nebulizers, and dry powder inhalers. Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations' stability.

Spherical agglomerates of lactose with enhanced mechanical properties.

The aim of this study was to prepare spherical agglomerates of lactose and to evaluate their physicochemical properties, flow properties, particle friability and compaction properties, and to compare them to commercially available types of lactose for direct compression (spray-dried, granulated and anhydrous β-lactose). Porous spherical agglomerates of α-lactose monohydrate with radially arranged prism-like primary particles were prepared exhibiting a high specific surface area. All types of lactose analysed had passable or better flow properties, except for anhydrous β-lactose, which had poor flowability.

Determination of Solubility Parameters of Ibuprofen and Ibuprofen Lysinate.

In recent years there has been a growing interest in formulating solid dispersions, which purposes mainly include solubility enhancement, sustained drug release and taste masking. The most notable problem by these dispersions is drug-carrier (in)solubility. Here we focus on solubility parameters as a tool for predicting the solubility of a drug in certain carriers.

Electrospun polycaprolactone nanofibers as a potential oromucosal delivery system for poorly water-soluble drugs.

The number of poorly water-soluble drug candidates is rapidly increasing; this represents a major challenge for the pharmaceutical industry. As a consequence, novel formulation approaches are required. Furthermore, if such a drug candidate is intended for the therapy of a specific group of the population, such as geriatric or pediatric, the formulation challenge is even greater, with the need to produce a dosage form that is acceptable for specific patients.

Mini-tablets: a contemporary system for oral drug delivery in targeted patient groups.

Introduction: Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles such as impaired swallowing and polypharmacy therapy, and also offering some therapeutic benefits such as dose flexibility and combined release patterns. Mini-tablets are a promising patient-friendly drug delivery system.

Areas Covered: Mini-tablets are tablets with a diameter ≤ 3 mm produced on conventional tablet presses equipped with multiple tooling.

Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system.

The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics.