A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants.

A fully liquid hexavalent containing Diphtheria (D), Tetanus (T) toxoids, whole cell Pertussis (wP), Hepatitis B (Hep B), type 1, 2, 3 of inactivated poliovirus (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (DTwP-HepB-IPV-Hib vaccine, HEXASIIL®) was tested for lot-to-lot consistency and non-inferiority against licensed DTwP-HepB-Hib + IPV in an open label, randomized Phase II/III study. In Phase III part, healthy infants received DTwP-HepB-IPV-Hib or DTwP-HepB-Hib + IPV vaccines at 6, 10 and 14 weeks of age. Blood samples were collected prior to the first dose and 28 days, post dose 3. Non inferiority versus DTwP-HepB-Hib + IPV was demonstrated with 95% CIs for the treatment difference for seroprotection/seroconversion rates. For DTwP-HepB-IPV-Hib lots, limits of 95% CI for post-vaccination geometric mean concentration ratios were within equivalence limits (0.5 and 2). Vaccine was well-tolerated and no safety concerns observed.Clinical Trial Registration - CTRI/2019/11/022052.

Exploring the potential of neem and tamarind gum as release retardants: Design and statistical optimisation of vildagliptin extended release matrix systems using D-optimal quadratic mixture design.

Exploring the significant role of natural polymers in developing drug delivery systems has been a promising area of research interest. The current investigation uses a D-optimal quadratic mixture design to design and evaluate neem and tamarind gum-based vildagliptin extended-release matrix tablets. Studying the combination effect of gums is one of the major objectives. Initial screening studies were performed to select the factors and their levels. The variables selected at different levels in mg/tablet are neem gum, tamarind gum, polyvinylpyrrolidone, and lactose monohydrate. Based on the screening experiments with both gums, the polymer content of 165 mg was chosen as the highest level in the DOE. Nineteen runs were generated to screen the desired parameters as responses. The total weight of the formulation was kept constant at 275 mg. Time (hours) required for 50 %, 90 % and 100 % of drug release and tablet hardness were selected as the responses for each run. The wet granulation method was adopted, and the critical variables were optimised using the design of experiments following Design Expert software. Statistical analysis was conducted, and the optimised formulations were prepared and evaluated to compare with the predicted responses. Stability studies were performed for the optimised batches. Results indicated that the prepared batches met the compendial limits and confirmed the application of neem and tamarind gum in the development of extended-release tablets of vildagliptin for 24 h. An optimised formulation comprising of 16.52 mg of neem gum and 148.48 mg of tamarind gum with a hardness of 7.5-8.5 kp produced 50 %, 90 % and 100 % drug release in 12, 22 and 25 h.

Comparison of the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children: an open-label, randomised, multicentre, non-inferiority, parallel-group, phase 3 trial.

Background: Considering the cholera menace in India and to seek licensure of the oral cholera vaccine (OCV), Euvichol-Plus, we conducted a clinical trial to compare the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children. Methods: This phase 3, open-label, multicentre, randomised, non-inferiority, parallel-group, comparative study was conducted at seven sites across India involving 416 healthy adults (aged ≥18-60 years) and children (aged ≥1 to <18 years). Healthy individuals who agreed to participate through a voluntary written informed consent form along with oral or written assent (for children aged 7-18 years) were included. No assent was required for those <7 years, as consent was given by the legally acceptable representatives (LAR). Participants were randomised 1:1 to receive two doses of either Euvichol-Plus or Shanchol orally, 14 days apart. The first dose (1.5 ml) was administered on visit 1, and the second dose at 2 weeks after the first dose during visit 2. Participants were followed up telephonically for 3 consecutive days after each visit and returned for final assessment at 2 weeks after the second dose (visit 3). Blood samples were collected for immunogenicity assessment, and safety analyses were done during all the visits. The primary immunogenicity endpoint was the percentage of participants with ≥4-fold increase in anti-Vibrio cholerae (V. cholerae) O1 Ogawa and O1 Inaba (vibriocidal) antibody titres at 2 weeks after the second dose as compared to baseline titres prior to dosing. The secondary immunogenicity endpoints included the percentage of participants with ≥4-fold increase in anti-V. cholerae O139 antibody titres at 2 weeks after the second dose as compared to baseline titres, and geometric mean titres (GMT) and geometric mean ratios (GMR) as measured by anti-V. cholerae O1 Ogawa, O1 Inaba, and O139 antibody titres at 2 weeks after the second dose as compared to baseline titres. The safety endpoints included assessment of solicited, unsolicited adverse events (AEs), and serious adverse events (SAEs). The clinical trial was registered with the Clinical Trials Registry of India (CTRI/2021/08/035344). Findings: The study was performed in two age cohorts: cohort 1 (aged ≥18-60 years, 208 participants [104 in Euvichol-Plus group and 104 in Shanchol group]), and cohort 2 (aged ≥1 to <18 years, 208 participants [104 in Euvichol-Plus group and 104 in Shanchol group]). A total of 414 participants (Euvichol-Plus: 206 and Shanchol: 208) who completed the study (intention-to-treat and per-protocol set) were analysed to compare the vibriocidal titre as an index for immunogenicity. At 2 weeks after the second dose, the percentage of participants in the Euvichol-Plus group who reported a ≥4-fold increase in anti-V. cholerae antibody titres were 68.93% (O1 Ogawa) [95% CI 62.13%-75.18%], 66.02% (O1 Inaba) [95% CI 59.11%-72.46%], and 59.71% (O139) [95% CI 52.67%-66.47%] as compared to 63.94% (O1 Ogawa) [95% CI 57.01%-70.47%], 65.87% (O1 Inaba) [95% CI 58.99%-72.28%], and 56.25% (O139) [95% CI 49.22%-63.10%] in the Shanchol group. The lower limit of 95% CI for treatment difference for all the antibody titres was ≥10% (non-inferiority margin), demonstrating that Euvichol-Plus was non-inferior to Shanchol. The post-vaccination GMT (Day 14 and 28) were more than the pre-vaccination GMT for all three serotypes in both groups. The GMR obtained for Euvichol-Plus over Shanchol for O1 Ogawa, O1 Inaba, and O139 serotypes was >1, indicating non-inferiority of Euvichol-Plus to Shanchol. The safety cohort included 416 participants. Headache was the most common solicited AE, whereas cold and cough were the most common unsolicited AEs in both groups. Interpretation: Euvichol-Plus appears to be non-inferior to Shanchol in terms of immunogenicity and safety in healthy Indian adults and children. Funding: Techinvention Lifecare Private Limited, Mumbai, India.

Temporomandibular pain.

Temporomandibular joint pain has various medical and dental etiological factors. The etiology of the temporomandibular joint pain is enigmatic, no single etiological factor is regarded as the cause. Its distribution is also not confined to a single area. This article presents the basic etiologic factors, its epidemiology, distribution of pain, classification of patients and the psychosocial behavior of patients suffering with temporomandibular pain. As overwhelming majority of medical and dental conditions/issues related to etiology of temporomandibular pain in patients have traditionally been presented and interpreted from the clinician's point of view.

Ethyl 4-(2-fur-yl)-2-oxochroman-3-carboxyl-ate.

The title compound, C(16)H(14)O(5), was prepared from the reaction of 3-carbethoxy-coumarin with furan in the presence of AlCl(3) as catalyst. In the crystal, inter-molecular C-H⋯O hydrogen-bonding inter-actions between four mol-ecules lead to a tetra-mer in the unit cell. The furan ring is anti-periplanar [C-C-C-O = 167.9 (13)°] and the ethoxy-carbonyl group is (-)anti-clinal [C-C-C-O = -128.6 (14)°] to the lactone ring.

Nimesulide-modified gum karaya solid mixtures: preparation, characterization, and formulation development.

Solid mixtures of nimesulide (NS) and modified gum karaya (MGK) were prepared to improve the dissolution rate of NS. The effect of drug-carrier ratio on dissolution rate of NS was investigated by preparing the solid mixtures of different ratios by cogrinding method. Solid mixtures were also prepared by physical mixing, kneading, and solid dispersion techniques to study the influence of method of preparation. Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and equilibrium solubility studies were performed to explain the results of in vitro dissolution rate studies. It was clearly evident from the results that the NS dissolution rate was dependent on the concentration of MGK in the solid mixtures, and optimum weight ratio was found to be 1:4 (NS:MGK). Though the dissolution rate of NS from all solid mixtures prepared by different methods improved significantly, maximum improvement in dissolution rate was observed with solid dispersions. The order of methods basing on their effect on dissolution efficiency is solid dispersion > kneading > cogrinding > physical mixing > pure NS. Tablets of pure drug and solid mixtures (1:4 w/w, NS:MGK) were prepared. Though the best results from the dissolution test were obtained for the tablets containing solid dispersions, tablets containing cogrinding mixture were found to be suitable, from a practical point of view, for commercialization.

Influence of colon degradation of polysaccharide on the oral bioavailability of theophylline from controlled release hydrophilic matrices.

Hydrophilic matrices of gum karaya (GK) and guar gum (GG) using theophylline (TH) as a model drug were prepared for oral controlled release. In vitro release studies were performed for these matrix systems to find out the suitable drug-carrier ratio, which extend the drug release up to 24 h. Promising matrix systems were subjected for in vitro degradation studies in the presence of rat caecal contents. These matrices were also evaluated for their in vivo performance in healthy human volunteers. Matrix systems containing 40% w/w of polysaccharide (GK or GG) have shown uniform and similar in vitro drug release profile for 24 h in the Sorenson's phosphate buffer (pH 7.4). However, TH release from GG-TH matrix system in the presence of rat caecal contents was significantly higher than that from GK-TH matrix system. This is because of the susceptibility of GG for degradation by microorganisms present in the rat caecal content. Though there was no significant difference between the peak plasma concentration (Cmax) and time of its occurrence (Tmax) for TH from GG-TH and GK-TH matrix systems, it was found that oral bioavailability of TH from former matrix was significantly higher than that of later. Therefore, the present study disclosed that the usage of colon degradable polymer offers an advantage in the design of controlled release dosage forms of drugs, which has good absorption properties throughout the gastrointestinal tract.