ABSTRACT
The use of hot-melt extrusion (HME) technique in the preparation of semi-solid products offers several advantages over conventional processes. However, the optimization of the technique for preparation of semi-solid pharmaceuticals is challenging due to involvement of ingredients with different physical properties. Hence, a simple tool to optimize the mixing of ingredients that results in a target ratio and drug content uniformity is utmost important. In this study, a handheld colorimeter has been explored to optimize the process variables of twin screw processor for preparation of hydrophilic PEG-based ointment. The process parameters which were optimized with use of handheld colorimeter have been used for preparation of polyethylene glycol-based metronidazole ointment. The metronidazole ointment prepared by twin screw processor was compared with commercially available metronidazole gel for in vitro release testing and ex vivo permeation. The flux, ex vivo bioavailability, and Tmax of polyethylene glycol-based metronidazole ointment was found to be similar to that of marketed metronidazole gel.
Subject(s)
Anti-Bacterial Agents/chemistry , Drug Compounding/methods , Hot Melt Extrusion Technology/methods , Metronidazole/chemistry , Ointments , Biological Availability , Freezing , Technology, Pharmaceutical/methodsABSTRACT
The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6-11s) and more than 95% dissolution in 5min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration.
Subject(s)
Anti-Allergic Agents/administration & dosage , Chlorpheniramine/administration & dosage , Drug Carriers/administration & dosage , Hot Temperature , Technology, Pharmaceutical/methods , Administration, Oral , Adolescent , Adult , Animals , Anti-Allergic Agents/chemical synthesis , Anti-Allergic Agents/metabolism , Chlorpheniramine/chemical synthesis , Chlorpheniramine/metabolism , Drug Carriers/chemical synthesis , Drug Carriers/metabolism , Drug Evaluation, Preclinical/methods , Female , Humans , Male , Rats , Rats, Sprague-Dawley , Solubility , Taste Perception/drug effects , Taste Perception/physiology , X-Ray Diffraction/methods , Young AdultABSTRACT
The objective of this study was to develop caffeine citrate orally disintegrating tablet (ODT) formulations utilizing hot-melt extrusion technology and evaluate the ability of the formulation composition to mask the unpleasant bitter taste of the drug using in vitro and in vivo methods. Ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to enhance drug release. A modified screw configuration was applied to improve the extrusion processability and to preserve the crystallinity of the API. The milled extrudates were subjected to dissolution testing in an artificial salivary fluid and investigations using e-tongue, to assess the extent of masking of bitter taste of the API. There was an insignificant amount of drug released from the formulation in the salivary medium while over 80% of drug released within 30 min in 0.1N HCl. ODTs were also developed with the extrudate mixed with mannitol and crospovidone. The quality properties such as friability and disintegration time of the ODTs met the USP specifications. The lead extrudate formulations and the ODTs prepared using this formulation were subjected to human gustatory evaluation. The formulations were found to mask the unpleasant taste of caffeine citrate significantly.
Subject(s)
Caffeine/adverse effects , Citrates/adverse effects , Taste/drug effects , Caffeine/chemistry , Cellulose/analogs & derivatives , Chemistry, Pharmaceutical , Citrates/chemistry , Drug Carriers , Drug Compounding , Humans , Plasticizers , Solubility , Tablets , Taste PerceptionABSTRACT
OBJECTIVES: The overall goal of this research was to produce a stable hot-melt extruded 'Antifungal Denture Adhesive film' (ADA) system for the treatment of oral candidiasis. METHODS: The ADA systems with hydroxypropyl cellulose (HPC) and/or polyethylene oxide (PEO) containing clotrimazole (10%) or nystatin (10%) were extruded utilizing a lab scale twin-screw hot-melt extruder. Rolls of the antifungal-containing films were collected and subsequently die-cut into shapes adapted for a maxillary (upper) and mandibular (lower) denture. RESULTS: Differential scanning calorimeter and powder X-ray diffraction results indicated that the crystallinity of both APIs was changed to amorphous phase after hot-melt extrusion. The ADA system, containing blends of HPC and PEO, enhanced the effectiveness of the antimicrobials a maximum of fivefold toward the inhibition of cell adherence of Candida albicans to mammalian cells/Vero cells. Remarkably, a combination of the two polymers without drug also demonstrated a 38% decrease in cell adhesion to the fungi due to the viscosity and the flexibility of the polymers. Drug-release profiles indicated that both drug concentrations were above the minimum inhibitory concentration (MIC) for C. albicans within 10 min and was maintained for over 10 h. In addition, based on the IC50 and MIC values, it was observed that the antifungal activities of both drugs were increased significantly in the ADA systems. CONCLUSIONS: Based on these findings, the ADA system may be used for primary, prophylaxis or adjunct treatment of oral or pharyngeal candidiasis via controlled release of the antifungal agent from the polymer matrix.
Subject(s)
Adhesives/chemistry , Antifungal Agents/administration & dosage , Candidiasis, Oral/drug therapy , Clotrimazole/administration & dosage , Nystatin/administration & dosage , Animals , Calorimetry, Differential Scanning , Cellulose/analogs & derivatives , Cellulose/chemistry , Chemistry, Pharmaceutical , Dentures , Microbial Sensitivity Tests , Polyethylene Glycols/chemistry , X-Ray DiffractionABSTRACT
The treatment of genetic diseases using therapeutic gene transfer is considered to be a significant development. This development has brought with it certain limitations, and the process of overcoming these barriers has seen a drastic change in gene delivery. Many metal ions such as Mg2+, Mn2+, Ba2+ and, most importantly, Ca2+ have been demonstrated to have significant roles in gene delivery. Recently, calcium phosphate alone, or in combination with viral and nonviral vectors, was found to exert a positive effect on gene transfer when incorporated in the colloidal particulate system, which is an advancing approach to gene delivery. This review elaborates on various successful methods of using calcium in gene delivery.
