Processability of AquaSolve™ LG polymer by hot-melt extrusion: Effects of pressurized CO2 on physicomechanical properties and API stability.

The objective of this study was to investigate the processability of AquaSolve™ hydroxypropyl methylcellulose acetate succinate L grade (HPMCAS LG) via hot-melt extrusion and to examine the effect of pressurized carbon dioxide (P-CO2) on the physicomechanical properties of efavirenz (EFA)-loaded extrudates. To optimize the process parameters and formulations, various physical mixtures of EFA (30%, 40%, and 50%, w/w) and HPMCAS LG (70%, 60%, and 50%, w/w), respectively, were extruded using a co-rotating twin-screw extruder with a standard screw configuration, with P-CO2 injected into zone 8 of the extruder. Thermal characterization of the extrudates was performed using differential scanning calorimetry and thermogravimetric analysis. Scanning electron microscopy was employed to study the morphology and porosity of the formulations. Notably, the macroscopic morphology changed to a foam-like structure by P-CO2 injection resulting in an increased specific surface area, porosity, and dissolution rate. Thus, HPMCAS LG extrusion, coupled with P-CO2 injection, yielded faster dissolving extrudates. Stability studies indicated that HPMCAS LG was able to physically and chemically stabilize the amorphous state of high-dose EFA. Furthermore, the milling efficiency of the extrudates produced with P-CO2 injection improved because of their increased porosity.

Stabilization of fenofibrate in low molecular weight hydroxypropylcellulose matrices produced by hot-melt extrusion.

The objective of this study was to improve the dissolution rate and to enhance the stability of a poorly water-soluble and low glass-trasition temperature (T(g)) model drug, fenofibrate, in low molecular weight grades of hydroxypropylcellulose matrices produced by hot-melt extrusion (HME). Percent drug loading had a significant effect on the extrudability of the formulations. Dissolution rate of fenofibrate from melt extruded pellets was faster than that of the pure drug (p < 0.05). Incorporation of sugars within the formulation further increased the fenofibrate release rates. Differential scanning calorimetry results revealed that the crystalline drug was converted into an amorphous form during the HME process. Fenofibrate is prone to recrystallization due to its low T(g). Various polymers were evaluated as stabilizing agents among which polyvinylpyrrolidone 17PF and amino methacrylate copolymer exhibited a significant inhibitory effect on fenofibrate recrystallization in the hot-melt extrudates. Subsequently immediate-release fenofibrate tablets were successfully developed and complete drug release was achieved within 5 min. The dissolution profile was comparable to that of a currently marketed formulation. The hot-melt extruded fenofibrate tablets were stable, and exhibited an unchanged drug release profile after 3-month storage at 40°C/75% RH.

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

An ethnobotanical survey of medicinal plants used in Terai forest of western Nepal.

BACKGROUND: Nepal Himalayas have been known as a rich source for valuable medicinal plants since Vedic periods. Present work is the documentation of indigenous knowledge on plant utilization as natural remedy by the inhabitants of terai forest in Western Nepal. METHODS: Study was conducted during 2010-2011 following standard ethnobotanical methods. Data about medicinal uses of plants were collected by questionnaire, personal interview and group discussion with pre identified informants. Voucher specimens were collected with the help of informants, processed into herbarium following standard methods, identified with the help of pertinent floras and taxonomic experts, and submitted in Department of Botany, Butwal Multiple Campus, Tribhuvan University, Nepal for future references. RESULTS: During the present study 66 medicinal plant species belonging to 37 families and 60 genera has been documented. These plants were used to treat various diseases and ailments grouped under 11 disease categories, with the highest number of species (41) being used for gastro-intestinal disorders, followed by dermatological disorders (34). In the study area the informants' consensus about usages of medicinal plants ranges from 0.93 to 0.97 with an average value of 0.94. Herbs (53%) were the primary source of medicine, followed by trees (23%). Curcuma longa (84%) and Azadirachta indica (76%) are the most frequently and popularly used medicinal plant species in the study area. Acacia catechu, Bacopa monnieri, Bombax ceiba, Drymaria diandra, Rauvolfia serpentina, and Tribulus terrestris are threatened species which needs to be conserved for future use. CONCLUSIONS: The high degree of consensus among the informants suggests that current use and knowledge are still strong, and thus the preservation of today's knowledge shows good foresight in acting before much has been lost. The connections between plant use and conservation are also important ones, especially as the authors note that neither the local inhabitants nor the government is addressing the potential loss of valuable species in this region.

Documentation and determination of consensus about phytotherapeutic veterinary practices among the Tharu tribal community of Uttar Pradesh, India.

PURPOSE: The aim of the present investigation was to document the phytotherapeutic knowledge and veterinary healthcare management practices among the Tharu tribal community of Uttar Pradesh, India and to determine the consensus of such practices, in order to evaluate the potential for new veterinary drugs of herbal origin. METHODS: This study was conducted in 2000-2004 using semistructured, open-ended questionnaires, informal interviews and group discussions with farmers engaged in animal husbandry. RESULTS: In the present study, 59 phytotherapeutic practices using 48 plant species were documented for management of 18 types of healthcare problems of domesticated animals. Crude drug formulations keep the animal healthy, increase lactation, and reduce estrus interval and puberty period to make them economically more important. There was great agreement among informants regarding phytotherapeutic uses of medicinal plants with factor of informants' consensus (F(IC)) value ranging from 0.84 to 1, with an average value of 0.94. CONCLUSION: Study reveals that there is great agreement among informants for the usages of Azadirachta indica A Juss, Bombax ceiba L, Bambusa arundinacea (Retz) Willd, Corianderum sativum L, Cuscuta reflexa Roxb, Datura metal L, Nelumbo nucifera Gaertn, and Parthenium hysterophorus L. These species may be used for the development of new, cheep, effective, and eco-friendly herbal formulations for veterinary healthcare management. Further investigation of these herbal formulations for veterinary healthcare management will require safety and efficacy testing. There is an urgent need to formulate suitable conservation strategies for wildly growing phytotherapeutics to overcome their depletion from natural resources and to make these practices more eco-friendly.