The oral route is preferred, as they are easy to handle and take by patients of all age groups. Telmisartan (TSN) is an antihypertensive drug¹ belongs to BCS-class II drug and low solubility results in low bioavailability (~45%)².

Among the various techniques of solubility enhancing, solid dispersion (SD) technique³ stands on the top priority as it is a simple, easy and efficient approach.

Water-soluble polymers viz., Poly Vinyl Pyrrolidone (PVP) K-30⁴, Poloxamer-188⁵ and Hydroxy Propyl Methyl Cellulose (HPMC) K4M⁶ were employed with a promising role in increasing the solubility of drugs. In the present examination, the SD were prepared by melting and solvent evaporation techniques.

MATERIALS AND METHODS:

Materials:

Telmisartan was gifted by Cipla Ltd, Bengaluru. PVP K-30, Poloxamer-188, HPMC K4M, Microcrystalline Cellulose, Talc, and Magnesium stearate were procured from SD Fine chemicals India. Double distilled water was used whenever appropriate.

Methods:

Designing of Solid dispersions

The various formulae of TSN-SD were shown in table 1.

Table 1: Various formulae and codes

Drug: Carrier	Ratio	Method of preparation	Formulation code
TSN: PB	1:1	Melting	SD-1
	1:3	Melting	SD-2
	1:5	Melting	SD-3
	1:7	Melting	SD-4
TSN: PB	1:1	Solvent evaporation	SD-5
	1:3	Solvent evaporation	SD-6
	1:5	Solvent evaporation	SD-7
	1:7	Solvent evaporation	SD-8

PB-Polymer blend [Equal portion of PVP K-30+ Poloxamer-188+(HPMC) K4M]

Preparation of solid dispersions:

Melting:

The polymers were melted based on their decreasing melting points (HPMC-K4M, PVP K-30 then Poloxamer-188) in a china dish, then TSN was dispersed in the molten mass with continual thrilling. The mixture was permitted to solidify at room temperature. The product was stored in a desiccator (ABG Initiatives, Hyderabad, Telangana) for 24 h and then crushed in a mortar (Aruna Scientific, Hyderabad, Telangana). Later the powder was allowed through # 60 sieve (ASTM E 11, Hyderabad, Telangana) to get uniform particle size⁷.

Solvent evaporation:

TSN and the polymer mix were taken as per table 1, dissolved in dichloromethane (DCM) and stirred until the DCM evaporated totally. The obtained mass was shifted to Cal. Chloride containing desiccators till it dries. The resulting solid mass was then crushed in a mortar and passed through # 60 sieve and stored in a desiccator till use⁸.

Preparation of solid dispersion tablets

The SD equivalent to 40 mg of TSN was made by direct compression into tablet form, after blending⁹ with constituents as described in table 2 by using 8 station tablet compression machine (Karnavati, India).

Table 2: Formulation of a tablet containing solid dispersions

Ingredients	Quantity per tablet
Solid dispersions equivalent to 40 mg of Telmisartan	150
Lactose	75
Starch	15
Micro Crystalline Cellulose	50
Magnesium stearate	5
Talc	5
Weight of the tablets	300

Evaluation:

Melting point:

The purity of TSN pure sample was confirmed by measuring melting point. The temperature at which TSN melts was recorded using melting point apparatus¹⁰ (MT-934).

Solubility studies:

Telmisartan (TSN) pure drug was tested for solubility in 0.1N HCl, water, pH 4.5 Acetate buffer, pH 6.8 and pH 7.4 Phosphate buffers¹¹.

Drug-excipients compatibility studies:

The DSC and FTIR studies were performed to find the interaction among the TSN and carriers used in the study.

Differential Scanning Calorimetry (DSC):

Pure TSN and 1:1 ratio of TSN: Polymer mix were exposed to the analysis. About 10 mg sample was taken in a DSC crucible and scanned at 50-300°C (DSC-50, Shimadzu, Japan).

Fourier-transform infrared (FTIR) spectroscopic study

The interactions between components of the SD were investigated using FTIR spectroscopy. The FTIR spectra of the TSN alone and in combination with carriers were documented by the FTIR spectrometer (Bruker) by scanning at 4000-400 cm⁻¹range.

Evaluation Telmisartan Solid Dispersions

The subsequent results were examined for TSN-SD.

Flow properties:

The TSN-SD were evaluated for flow constraints^{12, 13} viz., angle of repose, true and tapped densities, Carr’s Index, Hausner’s ratio.

Yield:

The % recovery¹⁴ comprises the weight of dried SD to the total weight of TSN and polymers used in making the SD.

Actual weight of the SD

% Yield = ––––––––––––––––––––––––––––––– × 100

Total weight of drug and excipients

Evaluation Telmisartan Solid Dispersion tablets:

The TSN-SD tablets were exposed to the following assessments.

Uniformity in size and shape.

The tablets were examined under a dissection microscope (DM-100) for their morphology.

Thickness:

The TSN-SD tablets were firmed between the jaws of Vernier Calipers (Qumos Enterprises, India) and thickness is examined in triplicate.

Uniformity in weight:

Every batch of TSN-SD tablets (20 quantity) was individually weighed with an electronic digital balance (Citizen, CY-104, Mumbai, India) and mean was measured and related to the individual tablet weights. The deviation in weights was premeditated and then crisscross with IP specifications (Limit ± 7.5% of mean weight) ¹⁶.

Hardness:

TSN-SD tablets were pressed with the spindle of Monsanto tablet hardness tester (Vinsyst Technologies, Mumbai). The force needs to break the tablets were recorded in triplicates¹⁵.

Friability:

Surface erosion may happen while tablet handling can be elucidated by Roche Friabilator. Pre weighed (10 tablets) (W _initial) and placed and rotated for 4 min at 25 rpm and the final weight of tablets (W_final) was dogged. The loss on friability was calculated by the following equation¹⁷.

W initial – W final

F= ––––––––––––––––––– × 100

W initial

Calibration curve:

100mg of TSN dissolves in pH 1.2 of 0.1 M HCl. A series of dilutions (2, 4, 6, 8 and 10µg/ml) were prepared scanned spectrophotometrically at 291nm then the measured the absorbance vs. concentrations which gives a calibration curve¹⁸.

Uniformity of drug content:

5 tablets of each batch weighed and powdered. 40mg of TSN dissolved in 100ml of 0.1 N HCl (pH 1.2). From this 0.5ml was diluted to 5ml with pH 1.2 of 0.1 N HCl. The absorbance was estimated at 291nm using a double beam UV-Visible spectrophotometer (Lab India, Mumbai). The content uniformity was calculated from Telmisartan standard calibration graph¹⁹.

In-vitro drug release studies:

The dissolution specifications were as below²⁰

· Apparatus used: USP-II dissolution test apparatus

· Dissolution medium: 0.1M HCl

· The volume of dissolution medium: 900ml

· Temperature: 37±0.5°C

· Speed of basket paddle: 50rpm

· Sampling intervals: 5 min

· Sample withdraws: 10ml

· Absorbance measured: 291nm

RESULTS AND DISCUSSION:

The melting point of pure TSN was observed as 263.2 ±2.36^oC, indicates the purity of the TSN sample. The TSN shown good solubility in 0.1N HCl (0.325±0.001µg/ml) compared in contrast to Water, Acetate buffer (pH4.5), Phosphate buffer (pH6.8) and Phosphate buffer (pH7.4).

The DSC thermograms of TSN with polymer mix were lifted to lesser temperature representing good impregnation of TSN with polymers used (figure 1).

The FTIR study discovered that the typical peaks and stretches of TSN pure drug were also found in TSN –polymer blend, indicates no negative incompatibility of TSN with carriers used. The FTIR spectra of TSN pure and polymers were shown in figure 2 and 3.

Figure 1: DSC thermograms of Telmisartan pure and with polymer mix

Figure 2: FTIR spectrum of pure Telmisartan

Figure 3: FTIR spectrum of Telmisartan with polymer mix

Table 3: Flow character specifications

Formulation	Flow properties
Formulation	Angle of repose (⁰)	Bulk Density	Tapped Density	Carr’s Index	Hausner Ratio
SD-1	29.07±0.17	0.785±0.02	0.801±0.03	1.997±0.06	1.020±0.04
SD-2	28.60±0.08	0.553±0.01	0.562±0.03	1.601±0.02	1.016±0.01
SD-3	27.44±0.05	0.536±0.02	0.543±0.02	1.289±0.04	1.013±0.03
SD-4	28.05±0.03	0.589±0.03	0.599±0.03	1.669±0.07	1.016±0.02
SD-5	25.35±0.02	0.625±0.05	0.636±0.02	1.729±0.08	1.017±0.01
SD-6	29.26±0.11	0.758±0.06	0.771±0.05	1.686±0.05	1.017±0.03
SD-7	28.52±0.09	0.524±0.04	0.532±0.02	1.503±0.09	1.015±0.02
SD-8	26.81±0.12	0.635±0.05	0.644±0.06	1.397±0.02	1.014±0.01

All values mentioned as mean ±SD; The number of trials (n=3)

Table 4: Physical Characteristics of Prepared solid dispersions

Formulation	Physical parameter
Formulation	Yield (%)	Thickness (mm)	Uniformity of weight (mg)	Hardness (cm²)	Friability (%)	Assay (%)
SD-1	89.2±0.82	5.10±0.02	301.2±2.84	6.8±0.26	0.19±0.01	99.5±1.20
SD-2	95.3±0.51	5.03±0.02	302.5±2.51	6.9±0.05	0.52±0.03	98.6±2.35
SD-3	98.1±0.90	5.10±0.02	299.6±6.32	6.5±0.08	0.41±0.04	99.8±1.45
SD-4	99.0±0.32	5.01±0.03	301.0±2.25	5.9±0.06	0.32±0.02	98.2±1.68
SD-5	97.8±0.69	5.02±0.01	300.1±0.94	5.8±0.08	0.44±0.01	98.8±2.48
SD-6	98.5±1.84	5.11±0.02	301.9±1.25	5.2±0.06	0.32±0.02	97.7±1.25
SD-7	99.1±1.12	5.02±0.02	302.3±2.64	6.6±0.02	0.12±0.01	96.9±0.97
SD-8	98.5±2.23	5.00±0.01	303.2±3.68	7.3±0.05	0.50±0.03	99.5±2.33

Values in mean ±SD; trials (n=3)

Figure 4: Solubility of Telmisartan and solid dispersions in various media

The solubility of TSN was found to be good in 0.1N HCl and decrease with an increase in pH of media. Among the tablets, SD-7 showed good solubility in 0.1 N HCl. The detailed description of solubility was shown in figure 4.

TSN followed Beer’s Lambert’s law at 2 to 10 µg/ml. The regression (R² value was observed to be 0.9998 with the slope of 0.0906x+0.0572. The assessment of Telmisartan was determined with this calibration curve.

TSN released from the tablet was initial burst within 10 min and the end of 1h the TSN was completely released. The dissolution of prepared tablets was found good in formulations containing TSN: polymer mix at the ratio of 1:5 (figure 5).

CONCLUSION:

In the examination HPMC-K4M, PVP K-30 and Poloxamer-188 combination was a good grouping as a carrier for making solid dispersions by taking Telmisartan as a model drug. The formulation SD-7 in the ratios 1: 5 prepared by solvent evaporation was observed to have good solubility and drug dissolution constrains.

ACKNOWLEDGMENTS:

We are thankful to Cipla Ltd, Bengaluru, for giving the gift sample of Telmisartan.

CONFLICT OF INTEREST:

No conflict of interest was declared by the authors.

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Received on 20.12.2019 Modified on 16.02.2020

Research J. Pharm. and Tech. 2021; 14(1):280-284.

DOI: 10.5958/0974-360X.2021.00050.0