Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy

The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. In this study, the residual crystallinity on ball milling of lactose monohydrate (LMH), for periods up to 90 min, was evaluated by thermo-analytical techniques (TGA, DSC) and terahertz spectroscopy (THz). In general, the results from one of the DSC analysis and the THz measurements agree showing a monotonous decrease in relative residual crystallinity with milling time (∼80% reduction after 60 min milling) and a slight increase at the 90 min time point. However, the estimates from TGA and two other methods of analyzing DSC curve do not agree with the former techniques and show variability with significantly higher estimates for crystallinity. It was concluded that, the thermal techniques require more complex treatment of the data in the evaluation of changes in crystallinity of a milled material (in particular to account for the de-vitrification and mutarotation of the material that inevitably occurs during the measurement cycle) while the analysis of THz data is more straightforward, with the measurement having no impact on the native state of the material

Synthesis and evaluation of pH dependent hydrogels for controlled release of Venlafaxine HCl

pH dependent hydrogel formulations of venlafexine HCl were prepared by free radical polymerization method using polyethylene glycol as polymer. Various samples were prepared with varying concentration of polymer, monomer and cross-linker to study their effect on gel swelling, diffusion characteristics and drug release. Swelling was found to be increased with increase in pH. Increase in acrylic acid concentration increases swelling while increase in cross-linker concentration has an opposite effect on swelling. Drug release study was performed in pH 1.2, 5.5 and 7.5 for 12 hours at 37 oC and drug release was found to increase in higher pH. Prepared hydrogel preparations were also characterized by PXRD, TGA, SEM and FTIR

Hydroxypropyl cellulose-based orally disintegrating films of promethazine HCl for the treatment of motion sickness

Purpose: To prepare and characterize orally disintegrating films (ODFs) of promethazine hydrochloride (HCl) for prompt treatment of motion sickness.Methods: Films were prepared by solvent casting method using hydroxypropyl cellulose (HPC) as film former and glycerin as plasticizer along with a saliva stimulating and sweetening agent. Nine different film formulations were prepared and evaluated for their characteristics including thickness, disintegration time, tensile strength and drug release behavior.Results: The prepared films were transparent and slightly sticky in nature with thickness that ranged from 0.22 mm to 0.29 mm and tensile strength of 0.56 N/cm² to 2.49 N/cm². The disintegration time of film formulations ranged from 26.3 to 52.7 s and a majority of formulations released approx. 80 % of the drug within 10 min with a non-Fickian diffusion pattern.Conclusion: The study concludes that the orally disintegrating films of promethazine HCl can be prepared using HPC as film former.Key words: Orally disintegrating films, Promethazine, Solvent casting, Motion sicknes

Use of off-label and unlicensed drugs in pediatric patients: A longitudinal prevalence survey from Lahore, Pakistan

Purpose: To assess the extent of use of unlicensed/off-label drug in the children hospitalized in The Children’s Hospital and Institute of Child Health, Lahore, Pakistan. Methods: A prospective prevalence study was carried out in the selected hospital. A total of 1946 pediatric patients were hospitalized during study period. The patients’ demographic data and unlicensed/off-label drug use were noted by the researcher using a structured questionnaire and then analyzed. Results: During the survey period, 102 (5.24 %) pediatric patients received at least one off-label drug/unlicensed drug. The unlicensed drug was administered to 65 patients (63.7 %) while off-label drug was administered to 37 patients (36.3%). Milrinone (23.5%) was the most frequently prescribed unlicensed drug. Conclusion: The administration of unlicensed/off-label drug to treat different diseases in pediatric population is widespread in the health facility studied. These findings will provide guidance to new researchers in clinical trials, especially on cardiovascular drugs, opioid analgesic, antiemetic and anticancer drugs

Correlation between molecular dynamics and physical stability of two milled anhydrous sugars: lactose and sucrose

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.The process of milling often results in amorphization and the physical stability of amorphous phase is linked with its molecular dynamics. This study focuses on a propensity of two disaccharides (lactose and sucrose) to amorphize on ball milling and the stability of the resultant amorphous phase. The amorphous content in milled sugars is estimated by Differential Scanning Calorimetry (DSC) and the stability was measured in terms of the tendency to recrystallize by Broadband Dielectric Spectroscopy (BDS). The results show that the amorphous content increases with milling time and is greater for lactose than sucrose. At the same degree of amorphization, sucrose recrystallize at temperature ∼15 °C higher than lactose, indicating higher stability. The molecular dynamics (beta relaxation process), suggest that milled sucrose is more stable with higher activation energy (∼9 kJ mol−1) than that of lactose. The moisture content of amorphous phase also impacts its molecular dynamics in terms of increase in activation energy as the moisture decrease with increasing the milling times. The study suggests a greater stability of amorphous sucrose and susceptibility of milled lactose to recrystallize, however, on extended milling when the moisture content decreases, lactose was seen to become relatively more stable

Solubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipients

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.The aim of this study was to enhance the kinetic solubility and dissolution rate of ibuprofen by co-milling with different excipients and to establish the underlying mechanism(s) for such enhancement. In the first-part, two excipients (HPMC and soluplus) were selected from seven, and the optimal ball-milling parameters of speed and time (18 Hz, 15 min) were determined based on solubility-enhancement and flow-ability criteria. In the second-part, co-milling of different weight-ratios of ibuprofen-to-excipient was carried out and solubility and dissolution rates were determined. Mechanisms of biopharmaceutical enhancement were studied by SEM, laser diffraction, DSC, and FTIR analysis of the co-mixtures. Ibuprofen solubility (0.09 mg/mL for un-milled) was increased by factors of 4–5 and 10–20 for HPMC and soluplus, respectively. The weakening of crystals, stabilization of the amorphous phase and an increase in solid-state hydrogen bonding are the likely mechanisms for this enhancement. Reductions in Q70% dissolution time were also observed, by a factor of 4 and 7 for ibuprofen:HMPC and ibuprofen:soluplus co-milled mixtures, respectively. Although, there were similar reductions in particle size, dispersibility and degree of amorphization in both mixtures, the higher dissolution rate for soluplus, over that for HPMC, must be due to the additional solubilization contribution to the kinetic solubility provided by soluplus

Development of ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain

A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach