Hard Gelatin Capsules Containing Hot Melt Extruded Solid Crystal Suspension of Carbamazepine for improving dissolution: Preparation and In vitro Evaluation.

Aqueous solubility is one of the key parameters for achieving the desired drug concentration in systemic circulation for better therapeutic outcomes. Carbamazepine (CBZ) is practically insoluble in water, is a BCS class II drug, and exhibits dissolution-dependent oral bioavailability. This study explored a novel application of hot-melt extrusion in the manufacture and development of a thermodynamically stable solid crystal suspension (SCS) to improve the solubility and dissolution rate of CBZ. The SCSs were prepared using sugar alcohols, such as mannitol or xylitol, as crystalline carriers. The drug-sugar blend was processed by hot melt extrusion up to 40 % (w/w) drug loading. The extruded SCS was evaluated for drug content, saturation solubility, differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), in vitro release, and stability studies. The physicochemical characterization revealed the highly crystalline existence of pure drug, pure carriers, and extruded SCS. FTIR analysis did not reveal any physical or chemical incompatibilities between the drug and sugar alcohols and showed a homogeneous CBZ distribution within respective crystalline carriers. The SEM micrographs of the solidified SCS revealed the presence of approximately 100 µm crystalline agglomerates. In vitro dissolution and solubility studies showed that the CBZ dissolution rate and solubility were improved significantly from both crystalline carriers for all tested drug loads. The SCSs showed no significant changes in drug content, in vitro release profiles, and thermal characteristics over 3 months of storage at accelerated stability conditions (40±2°C/75±5% RH). As a result, it can be inferred that the SCS strategy can be employed as a contemporary alternative technique to improve the dissolution rate of BCS class II drugs via HME technology.

Multicomponent crystalline solid forms of aripiprazole produced via hot melt extrusion techniques: An exploratory study.

Multicomponent crystalline solid forms (salts, cocrystals and eutectics) are a promising means of enhancing the dissolution behavior of poorly soluble drugs. The present study demonstrates the development of multicomponent solid forms of aripiprazole (ARP) prepared with succinic acid (SA) and nicotinamide (NA) as coformers using the hot melt extrusion (HME) technique. The HME-processed samples were characterized and analyzed using differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and HSM analyses revealed a characteristic single melting temperature in the solid forms, which differed from the melting points of the individual components. The discernible changes in the FTIR (amide C=O stretching) and PXRD results for ARP-SA confirm the formation of new crystalline solid forms. In the case of ARP-NA, these changes were less prominent, without the appearance or disappearance of peaks, suggesting no change in the crystal lattice. The SEM images demonstrated morphological differences between the HME-processed samples and the individual parent components. The in vitro dissolution and microenvironment pH measurement studies revealed that ARP-SA showed a higher dissolution rate, which could be due to the acidic microenvironment pH imparted by the coformer. The observations of the present study demonstrate the applicability of the HME technique for the development of ARP multicomponent solid forms.

3D printing in personalized drug delivery: An overview of hot-melt extrusion-based fused deposition modeling.

Advancements in pharmaceutical technologies have led to the personalization of therapies over the last decade. Three-dimensional printing (3DP) is an emerging technique in the manufacturing of pharmaceutical dosage forms because of its potential to create complex and customized dosage forms according to the patient's needs. Among the various 3DP techniques based on different functioning mechanisms, fused deposition modeling (FDM) 3D printing is a versatile and widely used method with advantages such as precision of quantity and the ability to incorporate different fill densities. This method is also economical and easily produces complex designs. Hot-melt extrusion (HME) is an established technique in pharmaceutical manufacturing that is utilized in the development of filaments which are used as "ink roll" or feedstock material in FDM 3D printing. This review discusses the various stages involved in FDM 3D printing, including feedstock filament preparation using HME, digital dosage form designs, filament characterization, and various novel applications, and future perspectives.

Development and optimization of hot-melt extruded moxifloxacin hydrochloride inserts, for ocular applications, using the design of experiments.

The current study sought to formulate sustained-release hot-melt extruded (HME) ocular inserts of moxifloxacin hydrochloride (MOX; MOX-HME) for the treatment of bacterial keratitis. The concentration of Eudragit™ FS-100 (FS) and propylene glycol (PG) used as polymer and plasticizer, respectively, in the inserts were optimized using the central composite design (CCD) to achieve sustained release. The inserts were characterized for weight, thickness, surface characteristics, pH, and in vitro release profile. The crystalline characteristics of MOX and surface morphology of the inserts were evaluated using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Furthermore, ex vivo permeation through rabbit cornea and stability of the optimized MOX-HME insert was investigated. The results demonstrate an inverse correlation between FS concentration and MOX release from the MOX-HME inserts, and a potential 24 h release. The optimized MOX-HME inserts were found to be stable at room temperature for four months, showing no significant change in drug content, pH and release profile. MOX converted into an amorphous form in the MOX-HME inserts and did not recrystallize during the study period. SEM analysis confirmed the smooth surface of the MOX-HME insert. The ex vivo studies revealed that the MOX-HME inserts provided a much prolonged transcorneal MOX flux as compared to the commercial ophthalmic solution and the immediate-release MOX-HME insert. The results indicate that MOX-HME inserts could potentially provide a once-a-day application, consequently reducing the dosing frequency and acting as an alternative delivery system in the management of bacterial infections.

Development of Curcumin-Loaded Solid Lipid Nanoparticles Utilizing Glyceryl Monostearate as Single Lipid Using QbD Approach: Characterization and Evaluation of Anticancer Activity Against Human Breast Cancer Cell Line.

BACKGROUND: Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. OBJECTIVE: SLNs were developed by using glyceryl monostearate as the single lipid in the presence of surfactant Poloxamer 188 and evaluated the efficiency of SLNs to load the therapeutic cargo, curcumin (CUR). METHOD: The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). RESULTS: The optimized formulation had a particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 µg/mL after 24 h treatment. Furthermore, the treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). CONCLUSION: The results provide a strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy.

Formulation optimization, characterization, and evaluation of in vitro cytotoxic potential of curcumin loaded solid lipid nanoparticles for improved anticancer activity.

The aim of the present research was to develop a novel, biocompatible, amenable to industrial scale up and affordable solid lipid nanoparticles (SLN) preparation of curcumin and evaluate the therapeutic efficacy in vitro using cancer cells. We have incorporated cholesterol as the lipid to prepare SLN along with the Poloxamer-188 as stabilizer. High shear homogenization was used to prepare the SLN and formulation was optimized using Quality by Design The optimized Chol CUR SLN exhibited a narrow size distribution with a particle size of 166.4±3.5nm. Percentage encapsulation (%EE) was found to be 76.9±1.9%. The SLN were further characterized by DSC, FTIR, XRD and drug release. In vitro cell studies in MDA-MB-231 (Human Breast cancer) cell line revealed that the Chol CUR SLN showed superior cytotoxicity and uptake in comparison to the free curcumin. Furthermore, Chol CUR SLN induced a significantly higher apoptosis compared to free CUR treatment. These results indicated that the curcumin encapsulated in Chol SLN was able to significantly improve the cytotoxic potential and induction of apoptosis in MDA-MB-231 cells. The promising result from our study could lead a further exploration of this nanoparticle formulation to be utilized clinically for cancer treatment.