PMC:7532132 / 19700-25556 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7532132","sourcedb":"PMC","sourceid":"7532132","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7532132","text":"DISCUSSION\nThe main aim of this study was to formulate a pharmaceutical film consisting of PVA and PHEA, using ibuprofen sodium as a model drug where an improvement of drug dissolution profile was expected. Furthermore, the effect of varying concentrations of PVA on film properties was examined. At first, physical-chemical characteristics of film were analyzed. Through SEM results, some differences in particle sizes of F5 and F6 films were highlighted. F5 film, which contained a lower concentration of PVA, had smaller particles compared to F6 film, which had a higher concentration of PVA and larger particles. Budhian et al. also found that increasing polymer concentration caused an increase in particle size (49), which further supports the findings of this study. According to literature, PVA should show a smooth, dense surface (50), while ibuprofen sodium should appear as smooth-surfaced rectangular crystalline structures (51). In SEM images obtained, it can be observed that particles had quite an irregular shape due to aggregation, which could also lead to differences in particle size.\nWhen formulating a drug to propose a novel drug delivery system, it is essential to investigate the presence of a bond between drug and polymer. ATR-FTIR spectra F5 and F6 with pure ibuprofen sodium showed main peaks of drug and no significant shifts of peaks which confirms that drug was incorporated within films. Drug morphology and particle size used to affect drug dissolution profile once formulated (22,52). DSC results obtained (Fig. 3) highlighted that PVA and ibuprofen sodium were maintained in crystalline forms. DSC thermographs of ibuprofen sodium showed a sharp endothermic peak at 101°C, and this was assigned to the melting of ibuprofen sodium crystals (53). These findings suggest that ibuprofen sodium solid state was unchanged during the formulation process by the presence of polymers showing lack of strong interactions between drug and polymers within the solid dispersion (54). Baek et al. conducted a study using an ibuprofen-loaded solid dispersion and also found that ibuprofen remained in an unaltered crystalline state after being incorporated within polymers (54). Drug remaining in a crystalline state is vital when formulating a solid microcrystalline dispersion due to the crystalline state being a thermodynamically favored state which makes it more stable than the amorphous state (55). The amorphous state has higher internal energy which can lead to higher dissolution rates but lower stability in terms of shelf-life and dissolution study reproducibility (56). However, not all studies have found results which support enhanced dissolution rate of the amorphous state. For instance, Jensen et al. found that crystalline carbamazepine had a faster dissolution rate than the amorphous form of carbamazepine (56). These conflicting results may be due to the unstable nature of amorphous compounds which can lead to recrystallization back into the crystalline state during storage or processing (57). This results in a loss of dissolution and solubility advantage of the amorphous state. Mainly, an amorphous dosage form of ibuprofen sodium was proved to have long-term stability issue and alteration of dissolution profile as determined by Mantas et al. (58).\nThe results from drug content studies indicate that the F5 film contained 6.82% of the drug, while F6 film contained 7.01% of the drug. This result was lower than the content of medicine expected to be in the film (10%). Small drug content could be due to method of preparation of drug content studies, which could have influenced content uniformity of films in experimental conditions used and is registered when the formulation is not provided with a stabilizer (19). Moreover, evaluation of PDI demonstrated that particles were not monodispersed in the polymer matrix. Woertz et al. conducted content uniformity studies on loperamide films. They found that some of the films had lower drug content than expected which could be attributed to numerous reasons, such as the concentration of polymer and drug used in films (59).\nThe literature stated that the dissolution rate of poorly soluble drugs improves when the drug is incorporated within polymeric carriers (60). This is due to a solid dispersion forming where the presence of hydrophilic polymers has several effects such as decreasing particle size of drug (61), which means the surface area is more extensive. The diffusion layer of each particle decreases in thickness which leads to a higher dissolution rate (52). Additionally, the dispersion of a drug within polymers is expected to increase drug wettability and also prevent drug aggregation, which will also lead to a faster dissolution rate (61). Increased drug wettability caused by water-soluble polymers is because of each drug crystal that is surrounded by soluble polymeric carriers which can readily dissolve and wet drug particle surface, which increases dissolution rate (62). Results obtained from in vitro dissolution studies (Fig. 5) confirmed this hypothesis as dissolution rate of ibuprofen sodium alone was slower, in comparison to dissolution rate when incorporated within the film. This was highlighted in drug release profile that at 15 min was 59%. When comparing this to F5 and F6 films, maximum drug release was 74% and 72% respectively. Dissolution profiles obtained also show a “spring and parachute,” where the pattern has a “spring” which is the initial dissolution of drug and then a “parachute” which refers to prolonged supersaturation of drug (63). Besides, F5 film had a faster dissolution rate due to smaller particles, which will increase surface area for dissolution (61).\nFig. 5 Dissolution profile of films and ibuprofen sodium a zoomed-in section of the first 60 min of dissolution and b full dissolution","divisions":[{"label":"title","span":{"begin":0,"end":10}},{"label":"p","span":{"begin":11,"end":1103}},{"label":"p","span":{"begin":1104,"end":3298}},{"label":"p","span":{"begin":3299,"end":4126}},{"label":"label","span":{"begin":5722,"end":5728}}],"tracks":[{"project":"2_test","denotations":[{"id":"33006710-17207944-28314","span":{"begin":718,"end":720},"obj":"17207944"},{"id":"33006710-18686079-28315","span":{"begin":937,"end":939},"obj":"18686079"},{"id":"33006710-30020788-28316","span":{"begin":1511,"end":1513},"obj":"30020788"},{"id":"33006710-22864741-28317","span":{"begin":1514,"end":1516},"obj":"22864741"},{"id":"33006710-21175199-28318","span":{"begin":1775,"end":1777},"obj":"21175199"},{"id":"33006710-22553061-28319","span":{"begin":2001,"end":2003},"obj":"22553061"},{"id":"33006710-22553061-28320","span":{"begin":2194,"end":2196},"obj":"22553061"},{"id":"33006710-20429826-28321","span":{"begin":2421,"end":2423},"obj":"20429826"},{"id":"33006710-7891297-28322","span":{"begin":2598,"end":2600},"obj":"7891297"},{"id":"33006710-7891297-28323","span":{"begin":2848,"end":2850},"obj":"7891297"},{"id":"33006710-16892209-28324","span":{"begin":3034,"end":3036},"obj":"16892209"},{"id":"33006710-25976316-28325","span":{"begin":4122,"end":4124},"obj":"25976316"},{"id":"33006710-23964164-28326","span":{"begin":4417,"end":4419},"obj":"23964164"},{"id":"33006710-22864741-28327","span":{"begin":4572,"end":4574},"obj":"22864741"},{"id":"33006710-23964164-28328","span":{"begin":4759,"end":4761},"obj":"23964164"},{"id":"33006710-26709621-28329","span":{"begin":5589,"end":5591},"obj":"26709621"},{"id":"33006710-23964164-28330","span":{"begin":5717,"end":5719},"obj":"23964164"}],"attributes":[{"subj":"33006710-17207944-28314","pred":"source","obj":"2_test"},{"subj":"33006710-18686079-28315","pred":"source","obj":"2_test"},{"subj":"33006710-30020788-28316","pred":"source","obj":"2_test"},{"subj":"33006710-22864741-28317","pred":"source","obj":"2_test"},{"subj":"33006710-21175199-28318","pred":"source","obj":"2_test"},{"subj":"33006710-22553061-28319","pred":"source","obj":"2_test"},{"subj":"33006710-22553061-28320","pred":"source","obj":"2_test"},{"subj":"33006710-20429826-28321","pred":"source","obj":"2_test"},{"subj":"33006710-7891297-28322","pred":"source","obj":"2_test"},{"subj":"33006710-7891297-28323","pred":"source","obj":"2_test"},{"subj":"33006710-16892209-28324","pred":"source","obj":"2_test"},{"subj":"33006710-25976316-28325","pred":"source","obj":"2_test"},{"subj":"33006710-23964164-28326","pred":"source","obj":"2_test"},{"subj":"33006710-22864741-28327","pred":"source","obj":"2_test"},{"subj":"33006710-23964164-28328","pred":"source","obj":"2_test"},{"subj":"33006710-26709621-28329","pred":"source","obj":"2_test"},{"subj":"33006710-23964164-28330","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ec93","default":true}]}]}}