Category: Formulation and Quality
Purpose: Acyclovir (ACV), an antiviral drug, is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. The biological availability of ACV is only 10–20%, when ingested by mouth. Also, ACV requires multiple dosing in order to maintain adequate plasma concentrations (1). The present study was aimed at preparing an ACV Gastro-retentive formulation by hot melt extrusion (HME) techniques with the use of CO2, an inert non-toxic pressurized gas, and sodium bicarbonate. This will prepare a porous and low density floating multi particulate system which will prolong the gastric residence time, reduce the number of dosages, improve bioavailability and therapeutic efficacy (2).
Methods: The gastro-retentive formulations were performed using HME techniques employing a twin screw extruder (16mm Prism Euro Lab Thermo Fisher Scientific). For the first approach (F1), pressurized CO2 was injected in the barrel of HME from zone 4 using the high-pressure regulator fitted with a pressure gauge. The physical mixture of polymer (Klucel® EF) and ACV (20% w/w) was uniformly blended using the V-shell blender (Maxiblend, Globe Pharm) and then fed into the extruder. For the second approach (F2), the uniformly blended physical mixture of polymer (Klucel® EF), ACV (20% w/w) and sodium bicarbonate (10% w/w) was fed into the extruder using the volumetric feeder. The temperature of the barrel was 140℃ with 100 rpm for both of the approaches. Thermal characterization of the extrudates was performed using Differential Scanning Calorimetry. Scanning Electron Microscopy was employed to study the morphology and porosity of the formulation. The samples were tested for drug content and floating ability. The in vitro release study was carried out using USP dissolution apparatus II in 900 mL 0.1 N HCl, with the temperature maintained at 37 ± 0.5℃ and a paddle rotation speed set to 75 rpm.
Results: It was observed macroscopically that the morphology of the extrudates was changed to a foam-like structure after injection of pressurized CO2. The sodium bicarbonate extrudates released CO2 in the media. Thus, the specific surface area for both the samples was increased which enhanced the dissolution rate. The drug content for the F1 and F2 samples was found to be 79.16 ± 1.28% and 87.31 ± 2.56%, respectively. Both the formulations were floating without lag time indicating the influence of pressurized CO2 and sodium bicarbonate. From the in vitro release study, it was observed that the F1 and F2 samples provide the sustained release of the ACV for up to 6 hours with 106.19 ± 0.02% and 107.11 ± 0.07%, respectively (Figure 1). The thermograms of ACV (Figure 2) showed a characteristic endothermic peak at 255℃. The sharp ACV peak disappeared in the processed formulation. The absence of peak indicates a transformation of ACV into amorphous form in the processed formulations after HME.
Conclusion: It was observed the ACV gastro-retentive formulations were successfully formulated using HME with pressurized CO2 and with the addition of sodium bicarbonate. The morphological changes in the extrudates increased the porosity and surface area. They provided a sustained release for 6 hours with 100% release of the drug.
Gauri Shadambikar– Graduate Student, University of Mississippi, Ocford, Mississippi
Mashan Almutairi– Grad Student, University of Mississippi, Oxford, Mississippi
Suresh Bandari– Post-doc, University of Mississippi, Oxford, Mississippi
Michael Repka– Professor, University of Mississippi, Oxford, Mississippi