Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation

Basic fibroblast growth factor (FGF-2) is a highly labile protein with strong potential for tissue engineering. The aim of this study was to develop FGF-2 formulations that are stable against physical stressors encountered in pharmaceutical processing and evaluation. Pharmaceutical excipients, alone or in combination, were added to aqueous FGF-2 (770 ng/mL) solution and the stability of the resulting solutions on storage at 4–37 °C was evaluated. Stability of the solutions to repeated freeze-thaw cycles and lyophilisation was also evaluated, as well as the stability of the lyophilised stabilised protein to storage at −4, 4 and 18 °C for up to 12 months. In all of these experiments FGF-2 was quantified by ELISA assay. The as-received FGF-2, when dissolved in water, was highly unstable, retaining only 50% of baseline protein content after 30 min at 37 °C or 1 h at 25 °C. By contrast, FGF-2 solutions prepared with 0.5% w/v methylcellulose (MC) and 20 mM alanine (formulation F5) or with 0.5% w/v MC and 1 mg/mL human serum albumin (HSA) (formulation F6) were highly stable, having residual FGF-2 content comparable to baseline levels even after 2 h at 37 °C and 5 h at 25 °C. F5 and F6 were also highly stable to repeated freeze-thaw cycles, with >99% of FGF-2 load remaining after the third cycle. In addition, F5 and F6 were stable to lyophilisation, and the lyophilised products could be stored at −4, 4 or 18 °C for at least 12 months, with less than 1% loss in mean FGF-2 content. Thus, FGF-2 solution is effectively stabilised against both thermal and processing stressors in the presence of MC and alanine (F5), or MC and HSA (F6). The resultant FGF-2 solutions may be applied as medicinal products or further processed into more advanced medicinal products, e.g., scaffolds, for wound healing and tissue regeneration.

STUDY OF EFFECT OF AYURVEDIC PHARMACEUTICAL PROCESSING NAMED SHODHANA AND MARANA ON THE CHEMICAL COMPOSITION AND CRYSTALLINE STRUCTURE OF METAL IRON AND IRON-CONTAINING MINERALS USING XRD AND XRF ANALYSIS

Objective: This study was designed to evaluate the effect of Ayurvedic pharmaceutical procedures Shodhana and Marana on the chemical composition of the raw material. Methods: Iron and four iron-containing minerals were subjected to Shodhana and Marana. For Shodhana, Loha (Iron), Suvarnamakshika (Copper pyrite) and Mandura (iron slag,) were repeatedly quenched sequentially in sesamin oil, buttermilk, cow’s urine, natural vinegar and herbal decoctions. Kasisa (green vitriol) was grinded in the juice of Eclipta Alba. For Marana, these materials were first grinded in prescribed liquids and then incinerated in closed earthenware caskets in measured pits. Powdered Gairika (red ochre) was roasted in Cow’s ghee for its Shodhana. Samples of Loha (iron)-L1, Samanya Shodhita Loha–L2, Vishesha Shodhita Loha–L3, Loha bahsma-L4, Mandura (iron slag)–M1, Shodhita Mandura–M2, Mandura bahsma–M3, Suvarnamakshika (copper pyrite)-S1, Shodhita Suvarnamakshika-S2, Suvarnamakshika bhasma-S3, Kasisa (green vitriol)-K1, Shodhita Kasisa-K2, Kasisa bahsma–K3, Gairika (red ochre)-G1 and Shodhita gairika-G2; were studied using XRF and XRD techniques. Results: XRD findings suggested that the Chemical nature, elemental composition and Crystaline lattice structure of each substance were altered after extensive processings. XRF studies confirmed the multi-elemental nature of the final products. Reduction in particle size and other morphological changes were observed in intermediate and finished products during each procedure. Conclusion: The study indicates that the composition of material is altered as a result of Ayurvedic pharmaceutical processing, ’Shodhana and Marana.

Impact of vertical succussion strokes vs. vortex potentization on droplet evaporation patterns obtained from Iscador Quercus 3x potency

Background Pharmaceutical processing of homeopathic potencies consists of consecutively performed dilution and succussion steps. While the dilution steps are well defined, the manner of performing the succussions varies broadly among potency producers. Aims To study the impact of potentization consisting in the performance of vertical succussion strokes vs. vortex-like flow on droplet evaporation patterns obtained from Iscador Quercus 3x (ISCQ 3x). Methodology ISCQ 3x was prepared in three following variants: potentized for 2.5 min (i) by application of mechanically performed vertical strokes, or (ii) hand-made vortex-like flows; or (iii) only diluted and not-succussed control. Droplet evaporation method was performed as described in (1); in short: droplets of the three ISCQ 3x variants were evaporated on microscope slides (56 droplets of each variant distributed on four slides were evaporated in one experimental repetition). The experimental setup robustness was monitored by means of positive systematic control experiments, where on all 12 slides droplets of the ISCQ 3x variant potentized by the application of strokes were evaporated. The experiments were repeated five times. The resulting droplet residues were photographed in magnification 100x; the patterns were analyzed by means of the Image J software for their grey level distribution and textural and fractal parameters. Results and discussion All three ISCQ 3x variants could be significantly differentiated regarding some textural and fractal parameters; most parameters differentiated between the variant potentized by means of vertical strokes and the control and vortex-potentized variants. Fractal and textural parameters ranked the samples differently. Control experiments showed a reasonable experimental setup robustness. Conclusion The potentization by performing mechanical strokes vs. hand-made vortex-like flows influenced some phenomenological aspects of droplet evaporation patterns. This might indicate that some changes occurred on substance level as consequence of the mechanical impact. Further studies are necessary in this field.

PHARMACEUTICAL PROCESSING AND STANDARDIZATION OF INDRA VATI

Ayurveda is the most ancient system of life, health and cure. It is highly evolved and codified system of life and health science, based on its own unique and original concepts and fundamental principles. Rasa shastra, which starts with a pledge to render a happy, healthy and prosperous life can be considered as an advanced stage of Indian system of medicine. Rasa shastra has large number varieties of Rasaushadhi aiding on Madhumeha (Diabetes Mellitus) but among them ‘Indra Vati’ is one of the significant ones. Though this preparation is not formulated by any pharmacy. CCRAS and DPT. of AYUSH declared standards for some Ayurvedic drugs and formulations in Ayurvedic Pharmacopoeia of India but there is no matter regarding standards of Indra Vati found in it. So, here an attempt has been made to see all the factors are integrated and a strategic approach to validate such a process for Indra vati preparation and Standardization in terms of Ayurvedic as well as Modern science and technology.

A PHARMACEUTICO-ANALYTICAL STUDY OF AMRITADYA GUGGULU

Aushadha Kalpana is prepared by different pharmaceutical processing applied to the crude drugs to get the desired therapeutic effects. Guggulu kalpana is one of them. Guggulu is the gummy resin of the Indian plant bdellium i.e. Commiphora mukul. Guggulu is always used after Shodhana to remove its impurities. So the process of Shodhana becomes imperative in different media. In addition to it, Shodhana of Guggulu in different media brings specific properties to Guggulu. Ayurvedic medicines are gaining increase in popularity worldwide for the treatment of various diseases in recent times. In the present study, Amritadya guggulu, one of the Guggulu preparation mentioned in Pidika, Bhagandara and Sthaulya like conditions in Chakkradatta, was prepared and analysed so as to prove the safety and efficacy of the drug. Aims and objectives: To develop standard operative procedure for preparation of genuine drug and to analyze the safety and purity of the drug. Material and Methods: Amritadya guggulu was prepared as per classical texts and analysed by using different parameters like organoleptic properties, physicochemical properties, TLC etc. Discussion and Conclusion: 50% weight loss was observed. The weight loss was due to removal of impurities present in the Guggulu and handling loss. Presence of low acid insoluble ash (1.08%) determines the presence of low adherent dirt as well as sand particles. Presence of low moisture content (loss on drying 6.2%) decreases decomposition and enhances the shelf life and therapeutic value of the drug. Hence it can be concluded that the pharmaceutical and analytical study confirm the authenticity and quality of the drug.

The crystal structure, morphology and mechanical properties of diaquabis(omeprazolate)magnesium dihydrate

The crystal structure of diaquabis(omeprazolate)magnesium dihydrate (DABOMD) in the solid state has been determined using single-crystal X-ray diffraction. Single crystals of DABOMD were obtained by slow crystallization in ethanol with water used as an antisolvent. The crystal structure shows a dihydrated salt comprising a magnesium cation coordinating two omeprazolate anions and two water molecules (W1) that are strongly bound to magnesium. In addition, two further water molecules (W2) are more weakly hydrogen-bonded to the pyridine nitrogen atom of each omeprazolate anion. The crystal structure was utilized to estimate key material properties for DABOMD, including crystal habit and mechanical properties, which are required for improved understanding and prediction of the behaviour of particles during pharmaceutical processing such as milling. The results from the material properties calculations indicate that DABOMD exhibits a hexagonal morphology and consists of a flat slip plane through the (100) face. It can be classed as a soft material based on elastic constant calculation and exhibits a two-dimensional hydrogen-bonding framework. Based on the crystal structure, habit and mechanical properties, it is anticipated that DABOMD will experience large disorder accompanied by plastic deformation during milling.

ARRONAX Cyclotron: Setting up of In-House Hospital Radiopharmacy

Whilst radiopharmaceuticals have an important role to play in both imaging and treatment of patients, most notably cancer patients, nuclear medicine and radiopharmacy are currently facing challenges to create innovative new drugs. Traditional radiopharmaceutical manufacture can be considered as either a routine hospital production or a large-scale industrial production. The gap between these two practices has meant that there is an inability to supply innovative radiopharmaceuticals for use at the local level for mono- or multicentric clinical trials with satisfactory quality and safety specifications. This article highlights the regulatory requirements in aseptic pharmaceutical processing and in nuclear medicine to be able to locally produce radiopharmaceuticals. We validate the proof-of-concept for an “in-house” hospital-based radiopharmacy including an on-site cyclotron, that can fulfill the conflicting requirements between radiation safety and aseptic processing. The ARRONAX in-house radiopharmacy is currently able to provide sterile and pyrogenic-free injectable radiopharmaceutical compounds for both industrial and institutional clinical trials.