Vacuum foam dried sugar-phosphate amorphous mixtures for stabilization of doxorubicin hydrochloride

The objective of the present study was to stabilize doxorubicin hydrochloride in sugar-phosphate amorphous mixtures at ambient temperature by drying it with vacuum foam drying. Finished products were evaluated for foam characteristic, residual moisture content, reconstitution time, percent drug recovery and drug-excipient interactions. FTIR studies revealed existence of physical interaction of drug with sugar. Light microscopy showed formation of amorphous glass which was supported by the observations of XRPD analyses. The optimized composition in vacuum foam drying was processed by lyophilization and their stability was compared. Storage at ambient temperature for 6 months showed that stability of vacuum foam dried product was better than lyophilized products. The amount of residual moisture affected the stability of drug. The detailed study revealed lactose and sodium dihydrogen phosphate is best suited for stabilization of doxorubicin hydrochloride at room temperature.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India

Effect of organogel components on in vitro nasal delivery of propranolol hydrochloride

The purpose of this research was to evaluate in vitro transnasal sustained-release ability of sorbitan monostearate (SMS) organogels in isopropyl myristate (IM). Organogels were prepared containing SMS (2.5%–20%) and water (5%–25%) in IM and analyzed microscopically for phase behavior. The effect of Tween surfactants on gel strength and in vitro nasal diffusion of propranolol is reported. The in vitro nasal release retardant effect of SMS and Tween 20 was investigated using factorial design. The microscopic changes in structure of organogel during in vitro nasal diffusion were studied. The water-holding capacity of SMS organogels in IM increased with SMS concentration. The release retardant effect with incorportation of cosurfactant was of the order of Tween 80> Tween 60> Tween 20. Gel strengthening and increased viscosity were evident with increased concentration of SMS and Tween 20. The 3-dimensional network of SMS molecules controls the diffusional drug release. The organogel system on nasal mucosa during diffusion is dynamic in nature and changes continuously with the time of diffusion. The water penetration in the organogel network results in percolation and emulsification of organogel, thus affecting the release. Organogels provided an effective barrier for diffusion of propranolol. The surface epithelium lining and the granular cellular structure of treated nasal mucosa were intact

The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial

Background Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). Methods In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry–India (CTRI/2022/06/043608) and is completed. Findings 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8–99·9) with Sii-PTCV and 100·0% (88·4–100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9–99·2) with Sii-PTCV and 100·0% (88·4–100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4–100·0) with Sii-PTCV and 3·3% (0·1–17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9–99·2) with Sii-PTCV and 0% (0·0–11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. Interpretation Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. Funding Serum Institute of India

Drug release properties of polyethylene-glycol-treated ciprofloxacin-Indion 234 complexes

The polyethylene glycol (PEG) treatment of ciprofloxacin-Indion 234 complex was aimed to retard rapid ion exchange drug release at gastric pH. Ciprofloxacin loading on Indion 234 was performed in a batch process, and the amount of K+ in Indion 234 displaced by drug with time was studied as equilibrium constant KDM. Drug-resin complex (DRC) was treated with aqueous PEG solution (0.5%–2% wt/vol) of different molecular weights (MWs) for 2 to 30 minutes. The PEG-treated ciprofloxacin-Indion 234 complex was evaluated for particle size, water absorption time, and drug release at gastric pH. During drug loading on Indion 234, the equilibrium constant (KDM) increased rapidly up to 20 minutes with efficient drug loading. Increased time of immersion of the drug resinate in PEG solutions significantly retained higher size particles upon dehydration. The larger DRC particles showed longer water absorption times owing to compromised hydrating power. The untreated DRC showed insignificant drug release in deionized water; while at gastric pH, ciprofloxacin release was complete in 90 minutes. A trend of increased residual particle size, proportionate increase in water absorption time, and hence the retardation of release with time of immersion was evident in PEG-treated DRC. The time of immersion of DRC in PEG-treated DRC. The time of immersion of DRC in PEG solution had predominant release retardant effect, while the effect of molecular weight of PEG was insignificant. Thus, PEG treatment of DRC successfully retards ciprofloxacin ion exchange release in acidic pH

Molecular properties of ciprofloxacin-indion 234 complexes

The purpose of this research was to formulate tasteless complexes of ciprofloxacin with Indion 234 and to evaluate molecular properties of drug complexes. The effect of batch and column process, complexation time, temperature, and pH on ciprofloxacin loading on Indion 234 is reported. Drug resin complexes (DRC) were characterized by infrared spectroscopy, thermal analysis, and x-ray diffraction pattern. Ciprofloxacin release from DRC is obtained at salivary and gastric pH and in the presence of electrolytes. The efficient drug loading was evident in batch process using activated Indion 234 with a drug-resin ratio of 1∶1.3. Drug complexation enhanced with pH from 1.2 to 6, while temperature did not affect the complexation process. Infrared spectroscopy revealed complexation of—NH (drug) with Indion 234. DRC are amorphous in nature. Drug release from DRC in salivary pH was insufficient to impart bitter taste. Volunteers rated the complex as tasteless and agreeable. Complete drug release was observed at gastric pH in 2 hours. The drug release was accelerated in the presence of electrolytes. Indion 234 is inexpensive, and the simple technique is effective for bitterness masking of ciprofloxacin

Vacuum foam drying for preservation of LaSota virus: Effect of additives

The purpose of this research was to apply vacuum foam drying (VFD) for processing of LaSota virus and to screen formulation additives for its stability. The aqueous dispersion of harvest containing sucrose or trehalose in combination with additive (monosaccharides, polymers, N-Z-amine) was prepared. The diluted dispersions in vials were vacuum concentrated, foamed to form a continuous structure, and vacuum dried. The products were evaluated for foam characteristics, residual moisture, virus titer, x-ray diffraction pattern, and stability profile. The foamability increased with solid content in solutions. The foamability of sucrose was enhanced with incorporation of N-Z-amine (10% and 15% wt/vol) and polyvinyl pyrrolidone (PVP K30, 3% wt/vol). The fructose- or galactose-containing mixtures were deposited irregularly on the vial surface. The virus titer increased with disaccharides in the formulation. Sucrose provided better protection than trehalose. Unlike lyophilization, N-Z-amine with sucrose protected the virus from Millard’s Browning. Amino acids do not have a catalytic effect on hydrolysis of sucrose during VFD. Monosaccharides were ineffective. A synergistic effect of PVP K30 or polyethylene glycol 6000 (3% wt/vol) with N-Z-amine provided the maximum virus titer (6.97 and 7.15, respectively). This formulation retained the desired virus potency at 5°, 25°, and 40°C. The diffraction pattern revealed that a threshold concentration of N-Z-amine was required for inhibiting crystallization of sucrose during VFD. VFD was successfully applied to produce a solid LaSota formulation. The products were amorphous and did not devitrify on storage