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Title: Properties of capsule shells made from hydroxypropyl methylcellulose (hypromellose)
Author: Solaiman, Amanda
ISNI:       0000 0004 2745 1696
Awarding Body: University of Sunderland
Current Institution: University of Sunderland
Date of Award: 2010
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Recently, hydroxypropyl methylcellulose (HPMC) has been made available as an alternative to gelatin for the manufacture of two-piece hard capsules. Hard Capsules manufactured from HPMC with carrageenan as a gelling agent have demonstrated rapid and comparable in-vivo disintegration times to gelatin and overcome some of the disadvantages gelatin capsules present. Gelatin becomes brittle when stored at low humidity and shell dehydration may occur with hygroscopic fillings. In addition, the presence of aldehyde groups in the filling material can reduce the solubility of the gelatin capsule shell by crosslinking. HPMC capsule shells demonstrate lack of brittleness even at moisture levels below 2%, no cross-linking and improved chemical stability, however there is a lack of information relating to the physico- chemical properties of HPMC capsule shells and their dissolution behaviour. The aims of this work were to develop and use different techniques to investigate the physicochemical properties of HPMC and gelatin hard capsule shells and to study the possible interactions between the capsule shell (after different storage conditions) and dissolution media (composition, pH and ionic strength) with and without filling materials. Thermal analysis was undertaken using MDSC to determine and compare the glass transition temperatures of gelatin and three batches of HPMC, which gave an insight into their fundamental physico-chemical properties. Rheological studies were undertaken using DMA, which is a novel method that has not been used previously on capsule shells, to investigate and compare the different viscoelastic properties of the capsules. These included: static scans to study the elastic modulus, linear creep to determine the behaviour of the capsule shells under stress, and dynamic scans to determine the storage modulus and viscosity. The influence of storage RH and time (35% and 53% RH for 24 hours and 3 days), dissolution media composition, ionic strength and pH on the shell dissolution time, and drug release properties of the capsules (using theophylline as the model drug) was also investigated. The findings show that the gelatin capsules became brittle at low moisture content and show some degree of aging upon storage, this was not seen for HPMC. Capsules made form HPMC were more elastic than gelatin and gelatin/Polyethylene glycol, with a greater degree of recovery to an applied stress (e.g. the Young’s Modulus for New HPMC and gelatin capsules was 0.728 MPa vs 1.092 MPa respectively after storage at 53%RH/3 days, and % JR for both capsules was 99.26% vs 98.47% respectively after storage at 35%RH/24 hr). It was also found that storage conditions showed no significant effect on the capsule shell dissolution time, and pH had minimal effect on shell dissolution time of the HPMC capsules. The Changes seen with change in pH were attributed to dissolution media composition, salt concentration and ionic strength of the different dissolution media. For HPMC shells, dissolution time in Sörensen phosphate buffer decreased by 13 – 22 % as pH increased from 5 to 8, however, in citro-phosphate buffer there was a 19 – 36 % increase in dissolution time from pH 5 to 7, In acetate buffer, HPMC shells did not dissolve in pH 6, whereas gelatin dissolution time increased from 2.0 to 3.5 mins as pH increased. Drug dissolution rate was highest from HPMC capsules in all 0.1 M 3 dissolution media compared with gelatin and was affected by the presence of high concentrations of K+ and Na+ ions, whereas gelatin capsules were influenced mostly by the presence of Na+ ions. For example in 0.1 M potassium phosphate buffer (KPB) 100% drug release from HPMC capsules occurred after 35 mins, however, this occurred after 180 mins for gelatin capsules, and in 0.1 M sodium phosphate buffer (NaPB) 100% drug release from HPMC and gelatin capsules occurred after 27 mins and 120 mins respectively. After 5 hours, < 4 % and 10 % drug release was obtained in 0.5 M KPB and NaPB respectively. The mechanism of drug release from gelatin capsules was found to be different in both basic and acidic media. This was constant for the HPMC capsules, showing that the change in pH did not affect the release mechanism. These investigations support work that has been previously reported concerning the properties of the HPMC capsules, and provide new information In terms of their viscoelasticity, interactions with various ions present in different dissolution media, drug dissolution behaviour before and after storage for prolonged periods, and the mechanisms of drug release.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pharmacy and Pharmacology