Investigation into the dosage form attributes of currently UK licensed cardiovascular and Parkinson's disease drug products

Globally, there is a continuous rise in the older population (over 65 years), particularly in developed countries. As many diseases are age-related, older adults represent a highly heterogeneous cohort. This presents a major challenge for both the pharmaceutical industry and healthcare professionals. The purpose of this research was to attract attention towards the appropriateness of geriatric formulations by investigating the dosage form attributes of currently UK licensed cardiovascular and Parkinson's disease drug products. Medication available in the UK for cardiovascular disorders and Parkinson's disease were screened and the available formulations, packaging and patient information leaflets of these medicines were analysed, with the goal of raising awareness of the need to cater for elderly patients with increasing difficulty in managing their medication. It emerged that although cardiovascular disorders and Parkinson's disease are more prevalent in older people, many treatment options have not been optimised for this cohort. In particular, older patient centred dosage forms, specific dosing requirements, excipients, patient-friendly packaging and easy-to-follow patient information were highlighted as areas to be considered in order to optimise health outcomes in the ageing population

Meeting commentary-"Medicines for older adults: Learning from practice to develop patient centric drug products"

A meeting jointly organised by the Academy of Pharmaceutical Sciences (APSGB), the Geriatric Medicine Society and the UCL School of Pharmacy took place on the 13th of March 2013, in Stevenage, UK [*]. The meeting was attended by a number of experts involved with the treatment and development of drugs for the older adult, including clinicians, pharmacists, academics, regulators and representatives from industry. The event created the platform to discuss the provision of medicines for older adults from a pharmaceutical sciences perspective

Patient centric formulations for paediatrics and geriatrics: Similarities and differences

Paediatrics and geriatrics both represent highly heterogenous populations and require special consideration when developing appropriate dosage forms. This paper discusses similarities, differences and considerations with respect to the development of appropriate medicine formulations for paediatrics and geriatrics. Arguably the most significant compliance challenge in older people is polypharmacy, whereas for children the largest barrier is taste. Pharmaceutical technology has progressed rapidly and technologies including FDCs, multi-particulates and orodispersible dosage forms provide unprecedented opportunities to develop novel and appropriate formulations for both old and new drugs. However, it is important for the formulation scientists to work closely with patients, carers and clinicians to develop such formulations for both the paediatric and geriatric population

Utilization of microfluidic V-junction device to prepare surface itraconazole adsorbed nanospheres.

Itraconazole is widely used as an anti-fungal drug to treat infections. However its poor aqueous solubility results in low bioavailability. The aim of the present study was to improve the drug release profile by preparing surface itraconazole adsorbed polymethylsilsesquioxane (PMSQ) nanospheres using a V-junction microfluidic (VJM) device. In order to generate nanospheres with rough surface, the process flow rate of Perfluorohexane (PFH) was set between 50 and 300 μl min(-1) while the flow rate of PMSQ and itraconazole solution were constant at 300 μl min(-1). Variations in the PFH flow rate enable the controlled size generation of nanospheres. PMSQ nanospheres adsorbing itraconazole were characterized by SEM, FTIR and Zetasizer. The release of itraconazole from PMSQ nanosphere surface was measured using UV spectroscopy. Nanosphere formulations with a range of sphere size (120, 320 and 800nm diameter) were generated and drug release was studied. 120nm itraconazole coated PMSQ nanospheres were found to present highest drug encapsulation efficiency and 13% drug loading in a more reproducible manner compared to 320nm and 800nm sized nanosphere formulations. Moreover 120nm itraconazole coated PMSQ nanospheres (encapsulation efficiency: 88%) showed higher encapsulation efficiency compared to 320nm (encapsulation efficiency: 74%) and 800nm (encapsulation efficiency: 62%) sized nanosphere formulations. The itraconazole coated PMSQ nanospheres were prepared continuously at rate of 2.6×10(6) per minute via VJM device. Overall the VJM device enabled the preparation of monodisperse surface itraconazole adsorbed nanospheres with controlled in vitro drug release profile

Modeling the physiological factors that affect drug delivery from a nipple shield delivery system to breastfeeding infants.

An apparatus was designed to mimic lactation from a human breast. It was used to determine the influence of milk fat content and flow rate, and suction pulse rate of a breastfeeding infant upon the release of a model compound from a nipple shield delivery system (NSDS). The NSDS would be worn by a mother to deliver drugs and nutrients to her infant during breastfeeding. Sulforhodamine B dye (SB) was used as model compound and formulated as a dispersible tablet to be placed within the NSDS. Increasing suction pulse rate from 30 to 120 pulses/min clearly correlated with increased cumulative release of SB for the same volume of milk passed through the NSDS. No distinct correlation was found between flow rates (1, 5, and 8 mL/min) and SB release, possibly because of competing factors controlling release rate at different flow rates. A highly similar SB release rate into two fat content fluids (2.9 and 4.2 wt %) was observed for identical flow conditions. This proof of concept study outlines a novel method to mimic lactation from a breast, and future studies will lead to effective methods to identify key physiological factors that influence drug release from a NSDS

Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project

Development of a model for robust and exploratory analysis of the rodent brief-access taste aversion data

The rodent brief-access taste aversion (BATA) model is an efficient in vivo screening tool for taste assessment. A new Emax (maximum effect attributable to the drug) model was developed and further investigated in comparison with three previously published models for analysing the rodent BATA data; the robustness of all the models was discussed. The rodent BATA data were obtained from a series of experiments conducted with a bitter reference compound, quinine hydrochloride dihydrate (QHD). A new Emax model that could be applied to both "lick numbers" and "lick ratios" was built and three published models that used lick ratios were employed for analysing the BATA data. IC50, the concentration that inhibits 50% of the maximum lick numbers, quantified the oral aversiveness of QHD. One thousand bootstrap datasets were generated from the original data. All models were applied to estimate the confidence intervals of the IC50s without symmetric assumption. The IC50 value obtained from the new Emax model was 0.0496mM (95% CI 0.0297-0.0857) using the lick numbers for analysis, while an IC50 of 0.0502mM (95% CI 0.0267-0.0859) was acquired with the lick ratios. Except one published model, the IC50 values have a similar range for the 95% CI. The new Emax model enabled the analysis of both "lick numbers" and "lick ratios" whereas other models could only handle data presented as "lick ratios". IC50s obtained with these two types of datasets showed similarity among all models thereby justified the robustness of the new Emax model

A mini-review of non-parenteral clonidine preparations for paediatric sedation

OBJECTIVE: To provide an overview of non-parenteral clonidine formulations and assess the feasibility of their use for paediatric sedation. / METHODS: A literature search was conducted using electronic databases and a combination of search terms. Forty articles met the inclusion criteria. Publications were grouped into different dosage forms and assessed for their potential application for sedation of children in intensive care. / KEY FINDINGS: Several routes of clonidine administration have been investigated for numerous indications in children, including perioperative sedation and analgesia. These include oral liquids, tablets, oral transmucosal systems, nasal sprays and rectal suspensions. Conflicting studies on oral transmucosal clonidine formulations suggest that further research is required to fully establish efficacy. Nasal sprays and rectal suspensions have the advantages of rapid onset of action and potential for dose flexibility, but predictable absorption is difficult to obtain. CONCLUSIONS: Provided age-appropriate strengths are available, IV formulations remain the most predictable in terms of bioavailability and flexible in terms of dose adjustment. However, as with all routes, down-titration is difficult given the long half-life of clonidine. Oral transmucosal systems, nasal sprays and rectal suspensions have potential in a less acute setting, but significant clinical work is required to elucidate a full pharmacokinetic and pharmacodynamic profile