Needle free injection technology - An overview

Needle free injection technology was developed to reduce the number of needle stick accidents and associated problems. A comprehensive literature review was completed regarding needle free injection technology and its applications, advantages over needle injections, their components and types such as powder injection, liquid injection, depot or projectile injection. This review describes needle free injection technology involving the generation of force by using compressed gas upon actuation in order to deliver a drug at very high speed through a nozzle. This review also describes injection methods that use a spring load jet injector, battery powdered jet injector, and gas powdered jet injector. An overview of marketed products, recent trends and other needleless drug delivery systems is given. Needle free injection technology is growing and has the potential to make the administration of medicine more efficient, safe and convenient.   Type: Commentar

Novel Biocompatible Honey Hydrogel Wound Healing Sponge for Chronic Ulcers

There is an ever-present need for non-allergenic antibacterial and antifungal wound dressing with a superior healing property for chronic ulcers. Among the entire modern wound healing dressings, hydrogel has a good capacity to donate moisture or absorb exudate and thereby providing a moist environment to facilitate wound healing process and at the same time protect the wound too. In the present study, povidne iodine loaded acrylamide based biocompatible biodegradable hydrogel dressings incorporating alginate, chitosan and gelatin showed good fluid absorbance capacity. The addition of honey showed improved tensile strength and moisture absorbance capacity of the hydrogel sponge. Apart from tensile strength, all the formulations were evaluated and compared for thickness, % elongation, folding endurance, swelling ratio, % of drug loading, thrombus formation, haemolysis assay and dispersion characteristics. Hydrogel containing chitosan and alginate showed better results in terms of tensile strength 4323gm/mm2, drug loading (27.17 %), thrombus formation (0.002 gm), drug release (97.99 %) and other parameters compared to gelatin based hydrogel. Wound healing study using well established wistar rat model showed complete healing of wound i.e. 98.28 % within 12 days. Povidone-Iodine and honey loaded acrylamide hydrogel with chitosan and alginate presented a very promising wound healing dressing. This honey hydrogel dressing can be a good alternative for infected chronic wounds and diabetic foot ulcers

Needle free injection technology - An overview

Needle free injection technology was developed to reduce the number of needle stick accidents and associated problems. A comprehensive literature review was completed regarding needle free injection technology and its applications, advantages over needle injections, their components and types such as powder injection, liquid injection, depot or projectile injection. This review describes needle free injection technology involving the generation of force by using compressed gas upon actuation in order to deliver a drug at very high speed through a nozzle. This review also describes injection methods that use a spring load jet injector, battery powdered jet injector, and gas powdered jet injector. An overview of marketed products, recent trends and other needleless drug delivery systems is given. Needle free injection technology is growing and has the potential to make the administration of medicine more efficient, safe and convenient.   Type: Commentar

Novel Biocompatible Honey Hydrogel Wound Healing Sponge for Chronic Ulcers

There is an ever-present need for non-allergenic antibacterial and antifungal wound dressing with a superior healing property for chronic ulcers. Among the entire modern wound healing dressings, hydrogel has a good capacity to donate moisture or absorb exudate and thereby providing a moist environment to facilitate wound healing process and at the same time protect the wound too. In the present study, povidne iodine loaded acrylamide based biocompatible biodegradable hydrogel dressings incorporating alginate, chitosan and gelatin showed good fluid absorbance capacity. The addition of honey showed improved tensile strength and moisture absorbance capacity of the hydrogel sponge. Apart from tensile strength, all the formulations were evaluated and compared for thickness, % elongation, folding endurance, swelling ratio, % of drug loading, thrombus formation, haemolysis assay and dispersion characteristics. Hydrogel containing chitosan and alginate showed better results in terms of tensile strength 4323gm/mm2, drug loading (27.17 %), thrombus formation (0.002 gm), drug release (97.99 %) and other parameters compared to gelatin based hydrogel. Wound healing study using well established wistar rat model showed complete healing of wound i.e. 98.28 % within 12 days. Povidone-Iodine and honey loaded acrylamide hydrogel with chitosan and alginate presented a very promising wound healing dressing. This honey hydrogel dressing can be a good alternative for infected chronic wounds and diabetic foot ulcers

Formulation and characterization of acyclovir based topical microemulsions by QBD approach

Objective: The proposed study is focussed at developing acyclovir microemulsions for topical drug delivery systems.  QbD was applied for better understanding of the process and to generate design space, using quality target product profile, critical quality attributes, and risk assessment. The aim of the experiment is to prepare a safe, efficacious, stable and patient compliant microemulsion dosage form of Acyclovir. Materials and methods: Pre-formulation studies were carried out which helped in developing a suitable dosage form. UV, FTIR and DSC studies were done for pre-formulation and post-formulation evaluations. QbD was applied to generate design space, using QTPP, CQA, and risk assessment. Microemulsions of acyclovir were developed by using 32 factorial designs. Pseudo terneary phase diagrams were constructed to screen various surfactants and co-surfactants for the preparation of microemulsions. Two independent variables Oil Concentration (X1) and Smix Concentration (X2) at three levels low, medium and high were selected and response surface plots were generated. The microemulsions were prepared by plotting pseudo terneary phase diagrams. Various characterizations that were carried out include % transmittance, Viscosity and % drug release. Statistical analyses of batches and surface response studies were done to understand the effect of various independent variables on the dependent variables. Results and Discussions: The λmax was confirmed at 251 nm by UV spectroscopy. The melting point was determined experimentally to be 2460C which confirms the drug to be Acyclovir. FTIR and DSC studies confirmed that the drug is Acyclovir.  Conclusion: The study indicates that microemulsions of Acyclovir by QbD approach were successfully developed. Keywords: Microemulsion, Acyclovir, DoE, Qb

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CURCUMIN AND CYCLOSPORINE BY RP-HPLC

Objective: The present work was undertaken with an aim to develop and validate a rapid reverse-phase high-performance liquid chromatography (RP-HPLC) method for the estimation of curcumin and cyclosporine in the capsule dosage form. Methods: The RP-HPLC method for the simultaneous estimation of curcumin and cyclosporine was developed using Agilent (Infinity 1260) HPLC system and Eclipse XDB-C18 (4.6 x 150 mm i.d., 5µ) stationary phase. The optimized mobile phase comprised of acetonitrile: water: methanol (50: 10: 40 v/v/v) pumped at a flow rate of 0.5 ml/min. Separation of drugs was achieved in an isocratic mode and elution was monitored using PDA detector at 214 nm. The method was validated as per ICH-Q2R1 guidelines. Results: Retention time of the curcumin and cyclosporine were found to be 3.073 min and 6.373 min with the correlation coefficient (R2) of 0.9993 and 0.998 respectively. The response of curcumin and cyclosporine was found linear in the concentration range of 8-48 μg/ml and 4-24 μg/ml respectively. The percent recovery values were found in the range of 97-103% indicating satisfactory accuracy of the method. The percent relative standard deviation (% RSD) values for the precision study was less than 2 which suggest that the method is precise. Conclusion: The proposed method was found accurate, precise and specific for the determination of curcumin and cyclosporine in bulk as well as in capsule dosage form. Thus, the present method can be used for routine analysis and quality control of curcumin and cyclosporine in bulk and capsule dosage form

Quality by Design based formulation and evaluation of acyclovir microsponges

Objective: The proposed study is focussed at developing acyclovir microsponges for oral drug delivery systems.  QbD was applied for better understanding of the process and to generate design space, using quality target product profile, critical quality attributes, and risk assessment. The aim of the experiment is to prepare a safe, efficacious, stable and patient compliant microsponge dosage form of Acyclovir. Materials and methods: Pre-formulation studies were carried out which helped in developing a suitable dosage form. UV, FTIR, DSC, and SEM studies were done for pre-formulation and post-formulation evaluations. QbD was applied to generate design space, using QTPP, CQA, and risk assessment. Microsponges of acyclovir were developed by 23 factorial designs. Three variables Drug: Polymer ratio (X1), Concentration of surfactant (X2) and Stirring speed (RPM) (X3) at two levels low and high were selected and response surface plots were generated. The microsponges were prepared by Quassi-emulsion solvent diffusion method. Various characterizations that were carried out include entrapment efficiency, percentage yield, particle size determination, in-vitro drug release studies and kinetic modelling of drug release. Statistical analyses of batches and surface response studies were done to understand the effect of various independent variables on the dependent variables. Results and Discussions: The λmax was confirmed at 251 nm by UV spectroscopy. The melting point was determined experimentally to be 2460C which confirms the drug to be Acyclovir. FTIR and DSC studies confirmed that the drug is Acyclovir. Eight trials were taken as per the by 23 factorial designs.  Conclusion: The study indicates that microsponges of Acyclovir by QbD approach were successfully developed. Keywords: Microsponge, Acyclovir, DoE, Qb

Engineering and manufacturing of probiotic E. Coli to treat metabolic disorder

The fields of synthetic biology and microbiome research developed greatly over the last decade. The convergence of those two disciplines is now enabling the development of new therapeutic strategies, using engineered microbes that operate from within the gut as living medicines. Inborn errors of metabolism represent candidate diseases for these therapeutics, particularly those disorders where a toxic metabolite causing a syndrome is also present in the intestinal lumen. Phenylketonuria (PKU), a rare inherited disease caused by a defect in phenylalanine hydroxylase (PAH) activity, is one such disease and is characterized by the accumulation of systemic phenylalanine (Phe) that can lead to severe neurological deficits unless patients are placed on a strict low-Phe diet. As an alternative treatment, Escherichia coli Nissle (EcN), a well-characterized probiotic, was genetically modified to efficiently import and degrade Phe (SYNB1618). The coupled expression of a Phe transporter with a Phe ammonia lyase (PAL) allows rapid conversion of Phe into trans-cinnamic acid (TCA) in vitro, which is then further metabolized by the host to hippuric acid (HA) and excreted in the urine. Experiments conducted in the enu2-/- PKU mouse model showed that the oral administration of SYNB1618 is able to significantly reduce blood Phe levels triggered by subcutaneous Phe injection. Decreases in circulating Phe levels were associated with proportional increases in urinary HA, confirming that Phe metabolism was caused by the engineered pathway in SYNB1618. Subsequent studies have shown that SYNB1618 is similarly operative in a non-human primate model, providing a translational link to inform future human clinical studies. Consistent with preclinical studies, recent Phase 1/2a clinical data demonstrate that oral administration of SYNB1618 resulted in significant dose-dependent production of biomarkers specifically associated with SYNB1618 activity, demonstrating proof-of-mechanism of this cell therapy

Engineering of probiotic E.coli to treat metabolic disorders

The fields of synthetic biology and microbiome research developed greatly over the last decade. The convergence of those two disciplines is now enabling the development of new therapeutic strategies, using engineered microbes that operate from within the gut as living medicines. Inborn errors of metabolism represent candidate diseases for these therapeutics, particularly those disorders where a toxic metabolite causing a syndrome is also present in the intestinal lumen. Phenylketonuria (PKU), a rare inherited disease caused by a defect in phenylalanine hydroxylase (PAH) activity, is one such disease and is characterized by the accumulation of systemic phenylalanine (Phe) that can lead to severe neurological deficits unless patients are placed on a strict low-Phe diet. As an alternative treatment, Escherichia coli Nissle (EcN), a well-characterized probiotic, was genetically modified to efficiently import and degrade Phe (SYN-PKU). The coupled expression of a Phe transporter with a Phe ammonia lyase (PAL) allows rapid conversion of Phe into trans-cinnamic acid (TCA) in vitro, which is then further metabolized by the host to hippuric acid (HA) and excreted in the urine. Experiments conducted in the enu2-/- PKU mouse model showed that the oral administration of SYN-PKU is able to significantly reduce blood Phe levels triggered by subcutaneous Phe injection. Decreases in circulating Phe levels were associated with proportional increases in urinary HA, confirming that Phe metabolism was caused by the engineered pathway in SYN-PKU. Subsequent studies have shown that SYN-PKU is similarly operative in a non-human primate model, providing a translational link to inform future human clinical studies. In addition to SYN-PKU, a second EcN strain was genetically engineered to rapidly import and degrade branched-chain amino acids (BCAAs) for the treatment of maple syrup urine disease (SYN-MSUD). MSUD, similar to PKU, is a rare genetic disorder caused by a defect in branched-chain ketoacid dehydrogenase activity leading to the toxic accumulation of BCAAs, particularly leucine, and their ketoacid derivatives. The controlled expression in SYN-MSUD of two BCAA transporters, a leucine dehydrogenase, a ketoacid decarboxylase and an alcohol dehydrogenase, result in the efficient degradation of BCAAs into branched-chain alcohols. In a mouse model of MSUD, the oral delivery of SYN-MSUD suppressed the increase in blood BCAAs level induced by a high-protein challenge and prevented the associated moribund phenotype, as measured by locomotor activity. In conclusion, the therapeutic effects observed with SYN-PKU and SYN-MSUD in pre-clinical studies support the further evaluation of engineered microbes as promising approaches for serious inborn errors of metabolism

APPLICATION OF 25 FACTORIAL DESIGN IN OPTIMIZATION OF SUPERPOROUS HYDROGEL SYNTHESIS CONTAINING NATURAL MUCILAGE

Objective: An experimental design, based on 25 factorial designs was used to study the influence of formulation parameters on a swelling and gelling behaviour of synthesized superporous hydrogel. Although a vast variety of formulations parameters could affect the hydrogel networks, attempt was made to synthesize a natural super-disintegrant, i.e., fenugreek mucilage, based super-porous hydrogel. Methods: A 25 factorial design was adopted to study the effect of various parameters for synthesis of superporous hydrogel using fenugreek mucilage as a foam stabilizer. The gelation features during the synthesis process, including inhibition period, exothermic period were observed. For this study, five formulation variables i.e, type of monomer, amount of cross-linker, redox initiator, redox activator and level of foam strengtheners were chosen and their effects were examined within the frame of a 25 factorial design. Results: The responses examined were inhibition period, exothermic period and gelling feature along with the physical appearance during gelation and after drying. These responses found to be dependent on the concentration of cross-linker and redox activator (P< 0.05). The resultant hydrogel was subjected to SEM study and it clearly showed that fenugreek mucilage at higher level could stabilise the foam during gelation process which led to better and enhanced porous network formation. Conclusion: The synthesized superporous hydrogels can be used in for those formulations where fast swelling and superabsorbent properties are critical