Formulation and evaluation of novel solid lipid microparticles as a sustained release system for the delivery of metformin hydrochloride

Figures & data

Table 1. Quantities of material used for SLMs formulation.

Batch	PEG-4000 (g)	Poloxamer-188(g)	MTH (mg)	Lipidmatrix (g)	Distilled water, q.s. (g)
A1	0.5	2.0	500	4.5	100
A2	1.0	2.0	500	4.0	100
A3	1.5	2.0	500	3.5	100
A4	2.0	2.0	500	3.0	100
B1	0.5	2.0	250	4.5	100
B2	1.0	2.0	250	4.0	100
B3	1.5	2.0	250	3.5	100
B4	2.0	2.0	250	3.0	100
C1	0.5	2.0	–	4.5	100
C2	1.0	2.0	–	4.0	100
C3	1.5	2.0	–	3.5	100
C4	2.0	2.0	–	3.0	100

Batches A1–A4 contain 500 mg of MTH, batches B1–B4 contain 250 mg of MTH, while batches C1–C4 contain no API.

Figure 1. DSC thermogram of (a) goat fat/Phospholipon® 90H blend, (b) Phospholipon® 90H and (c) goat fat.

Figure 2. Time-resolved particle size analysis of the SLMs. A1–A4 contain 500 mg of MTH, B1–B4 contain 250 mg of MTH while C1–C4 contain no API. Points represent mean ± SD (n = 3).

Table 2. Results of characterization of SLMs.

					pH analysis
Batch Code	% EE	PDI	% DL	ZP	24 h	1 month	2 months
A1	88.6	0.388	29.1	−48.00	6.7	7.1	7.2
A2	80.4	0.367	20.3	−39.10	6.7	7.1	7.2
A3	76.6	0.400	21.0	−26.11	4.7	5.8	5.8
A4	75.5	0.379	22.7	−38.20	5.4	5.6	6.2
B1	84.9	0.390	24.1	−41.10	4.3	4.7	6.9
B2	73.9	0.366	14.9	−34.00	4.8	4.7	5.0
B3	68.7	0.397	14.6	−23.10	3.9	4.9	5.3
B4	65.2	0.394	15.5	−30.01	4.0	4.1	4.3
C1	–	0.498	–	−29.13	4.2	4.9	5.1
C2	–	0.510	–	−36.21	5.1	5.2	4.9
C3	–	0.547	–	−18.81	5.0	5.0	5.2
C4	–	0.569	–	−22.03	5.2	5.3	5.7

BC = batch code, EE = % encapsulation efficiency, DL = % drug loading and ZP = Zeta potential.

Figure 3. Representative of the morphology of the SLMs. A1, B1 and C1 contain 500 mg of MTH, 250 mg of MTH and no API, respectively.

Figure 4. Percentage drug release from SLMs, (a) Batch A formulations containing 500 mg of MTH; (b) batch B formulations containing 250 mg of MTH. Points represents mean ± SD (n = 3).

Table 3. Kinetics of release of MTH from SLMs in phosphate buffer.

Batch code	Zero- order (r^2)	First- order (r^2)	Higuchi square root (r^2)	Korsmeyer– Peppas (r^2)	Hixon– Crowel (r^2)
A1	0.996	0.882	0.997	0.898	0.996
A2	0.990	0.762	0.998	0.889	0.999
A3	0.957	0.884	0.997	0.908	0.992
A4	0.981	0.689	0.999	0.928	0.995
B1	0.891	0.882	0.999	0.878	0.998
B2	0.977	0.887	0.999	0.983	0.996
B3	0.996	0.688	0.996	0.919	0.995
B4	0.972	0.899	0.999	0.978	0.999

Figure 5. Changes in blood glucose levels after oral administration of control and the SLMs, NS = normal saline, PM = pure metformin HCl, A1 = MTH-loaded SLMs (500 mg), B1 = MTH-loaded SLMs (250 mg), C1- unloaded SLMs and MS = marketed sample (mean ± SD, n = 5).