Thuốc bột cốm 2019 thuốc rắn đường uống đh dược Hà Nội

The quantity of water adsorbed to the crystal surface is small, b Water sorption isotherm for amorphous lactose, showing a rise to about 11% water content due to absorption, followed by

CÁC DẠNG THUỐC RẮN DÙNG QUA ĐƯỜNG UỐNG

Solid oral dosage forms

TÀI LIỆU HỌC TẬP

1   Bộ Y Tế (2006), Kỹ thuật bào chế và sinh

dược học các dạng thuốc, tập 2, nhà xuất bản Y học

2   Bộ môn Bào chế (2012), Thực tập bào chế,

Trường đại học Dược Hà Nội

3   Bộ môn Bào chế (2013), Bộ câu hỏi trắc

nghiệm môn Bào chế và SDH, Trường đại

TÀI LIỆU THAM KHẢO CHÍNH

1   David Jones (2008), Pharmaceutics- Dosage

form and design, London- Chicago

THUỐC BỘT- THUỐC CỐM

Phần 1:

Định nghĩa (DĐVN V):

“Là dạng thuốc rắn, gồm các hạt nhỏ, khô tơi,

có độ mịn xác định, có chứa một hay nhiều loại dược chất”…

Phân biệt 2 khái niệm: Bột thuốc - Thuốc bột

Thuốc bột

Một số đặc tính của tiểu phân chất rắn vận dụng

trong bào chế (thuốc bột, viên nén, viên nang cứng)

1.  Kích thước tiểu phân (KTTP)

2.  Hình dạng tiểu phân

3.  Lực liên kết tiểu phân

4.  Dạng thù hình

v   KTTP > 250 mc m: Bột chảy tốt

2 KTTP ảnh hưởng đến khả năng trơn chảy

Độ trơn chảy

Đo góc nghỉ

3/7/19 BM Bào chế

PARTICLE SCIENCE AND POWDER TECHNOLOGY

The different methods may produce different values

for the same powder, although these may be

self-con-sistent It is also possible that different angles of

repose could be obtained for the same powder, owing

to differences in the way the samples were handled prior to measurement For these reasons, angles of repose tend to be variable and are not always repre- sentative of flow under specific conditions.

I Table 14.2 Methods of measuring angle of repose

Apparatus Method Angle defined Apparatus < Method Angle defined

Fixed height cone

Angle of repose

Fixed base cone Angle of repose

Drained angle

of repose Ledge

Crater Drained angle of

V chøa trong bao

Lç xèp

3 KTTP ảnh hưởng đến KLR và độ xốp

Hình dạng tiểu phân

(f) (e)

(d)

•  Các tiểu phân càng gần hình cầu càng dễ trơn chảy (a), (b)

•  Rìa tiểu phân càng nhẵn càng dễ trơn chảy (a), (b)

- Lực kết dính: tiểu phân- tiểu phân

LỰC LIÊN KẾT TIỂU PHÂN

- Dạng vô định hình dễ tan hơn dạng kết tinh

-   Dạng kết tinh có nhiều loại

DẠNG THÙ HÌNH

PARTICLE SCIENCE AND POWDER TECHNOLOGY

surrounded by disorder, so they are described assemicrystalline For materials such as these it will not

be possible to produce a completely crystallinesample; however, the degree of crystallinity can varydepending upon processing conditions This canaffect the properties of the material and hence howthey function in pharmaceutical products

For low molecular weight materials the phous form may be produced if the solidificationprocess was too fast for the molecules to have achance to align in the correct way to form a crystal(this could happen when a solution is spray-dried)

amor-Alternatively, a crystal may be formed but thenbroken, for example if the crystal were exposed toenergy, such as milling A simple analogy that can beused here is that a crystal is like a brick wall, whichhas ordered long-range packing If the wall is hithard, perhaps during demolition, the bricks will sep-arate (Figure 9.6) Unlike the brick wall, however, adisrupted crystal will be unstable and will revertback to the crystal form This conversion may berapid or very slow and, as with polymorphism, itspharmaceutical significance will depend on how longthe partially amorphous form survives

Amorphous forms have a characteristic ture at which there is a major change in properties

form will be brittle and is described as the glassy

point where the molecules in the glass exhibit amajor change in mobility The lack of mobility whenthe sample is glassy allows the amorphous form to

storage temperature the increased molecular ity allows rapid conversion to the crystalline form.The glass transition temperature of an amorphousmaterial can be lowered by adding a small molecule,called a plasticizer, that fits between the glassy mole-cules, giving them greater mobility Water is a goodplasticizer for many materials, and so the glass tran-sition temperature will usually reduce in the pres-ence of water vapour Most amorphous materials areable to absorb large quantities of water vapour.Absorption is a process whereby one moleculepasses into the bulk of another material and shouldnot be confused with adsorption, which is whensomething concentrates at the surface of anothermaterial Figure 9.6 shows the way in which watercan access amorphous regions Figure 9.7 shows theamount of water that is adsorbed to a crystallinematerial (Figure 9.7(a)), compared to that absorbedinto an amorphous form of the same material(Figure 9.7(b)) It can be seen that the amountabsorbed is many times greater than that adsorbed.This large difference in water content at any selectedrelative humidity is important in many materials Forexample, it is possible that certain drugs can degrade

mobil-by hydrolysis when amorphous, but remain stablewhen crystalline The extent of hydrolysis of anantibiotic which had been processed to yield differ-ent levels of crystalline:amorphous forms is shown inTable 9.1; the extent of degradation is greater whenthe amorphous content is increased

In Figure 9.7 it can be seen that the amorphousform absorbs a very large amount of water until50% RH, after which there is a weight loss, thereason for which is that the sample has crystallized.Crystallization occurs because the absorbed waterhas plasticized the sample to such an extent that the7g has dropped below room temperature andallowed sufficient molecular mobility that the mole-cules are able to align and crystallize The water islost during this process, as absorption can onlyoccur in the amorphous form and so cannot endure

Table 9.1 The chemical stability of cephalothin sodium related to the amorphous content of the sample Data derived from Pikal et ai 1978

3/7/19 BM Bào chế

DẠNG THÙ HÌNH

SOLID-STATE PROPERTIES

Fig 9.7 (a) A water sorption isotherm for crystalline lactose

monohydrate The quantity of water adsorbed to the crystal

surface is small, (b) Water sorption isotherm for amorphous

lactose, showing a rise to about 11% water content due to

absorption, followed by water loss as the sample crystallizes

and the absorbed water is expelled.

into the crystalline state However, some water is

retained in this example (Fig 9.7(a) and (b)),

because lactose is able to form a monohydrate The

amount of water required to form a monohydrate

with lactose is 5% w/w (calculated from the

mole-cular weight of lactose and water), which is much

less than the 11 % that was present in the amorphous

form (Figure 9.7(b)).

In Figure 9.8 the amorphous content of lactose is

seen to increase in proportion to the length of time it

was left in an air-jet mill (micronizer) In Figure 9.9

it can be seen that a drug substance became partially

amorphous when treated in a simple ball mill, and

extensively amorphous when micronized Although

the example in Figure 9.9 is an extreme behaviour it

is not unusual for highly processed materials to

become partially amorphous Although milling does

not necessarily make all materials partially phous, the chance of seeing disruption to the crys- talline lattice will increase with the amount of energy used in the milling.

amor-The fact that processing can make crystalline materials partially amorphous means that it is possi- ble for very complex materials to form that contain different metastable states For example, in Figure 9.3 the plasma levels of two polymorphs of chloram- phenicol palmitate were shown, however if the j3- polymorph were milled it is possible that it might also become partially amorphous, which could make the plasma level even higher than when the crystalline form were used However, milling the /3-polymorph could also provide the necessary energy to convert it

to the stable a-polymorph, which would reduce the effective plasma level Equally, milling could disrupt the a-polymorph, giving a partially amorphous form that might have a higher bioavailability than the crystal In other words, the effect of processing on the physical form can be very complicated, and often unpredictable It is possible to produce a physical form that is partially amorphous and partially crys- talline The crystalline component could then be

Fig 9.8 The amorphous content induced in crystalline lactose

as a consequence of milling in an air-jet mill at different air pressures (Redrawn from Briggner et al 1994, with permission.)

Fig 9.9 The amorphous content of a model drug substance

following milling in a ball mill and a micronizer (Redrawn from Ahmed et al 1996, with permission.)

SOLID-STATE PROPERTIES

Fig 9.7 (a) A water sorption isotherm for crystalline lactose

monohydrate The quantity of water adsorbed to the crystal surface is small, (b) Water sorption isotherm for amorphous lactose, showing a rise to about 11% water content due to absorption, followed by water loss as the sample crystallizes and the absorbed water is expelled.

into the crystalline state However, some water is retained in this example (Fig 9.7(a) and (b)), because lactose is able to form a monohydrate The amount of water required to form a monohydrate with lactose is 5% w/w (calculated from the mole- cular weight of lactose and water), which is much less than the 11 % that was present in the amorphous form (Figure 9.7(b)).

In Figure 9.8 the amorphous content of lactose is seen to increase in proportion to the length of time it was left in an air-jet mill (micronizer) In Figure 9.9

it can be seen that a drug substance became partially amorphous when treated in a simple ball mill, and extensively amorphous when micronized Although the example in Figure 9.9 is an extreme behaviour it

is not unusual for highly processed materials to become partially amorphous Although milling does

not necessarily make all materials partially phous, the chance of seeing disruption to the crys- talline lattice will increase with the amount of energy used in the milling.

amor-The fact that processing can make crystalline materials partially amorphous means that it is possi- ble for very complex materials to form that contain different metastable states For example, in Figure 9.3 the plasma levels of two polymorphs of chloram- phenicol palmitate were shown, however if the j3- polymorph were milled it is possible that it might also become partially amorphous, which could make the plasma level even higher than when the crystalline form were used However, milling the /3-polymorph could also provide the necessary energy to convert it

to the stable a-polymorph, which would reduce the effective plasma level Equally, milling could disrupt the a-polymorph, giving a partially amorphous form that might have a higher bioavailability than the crystal In other words, the effect of processing on the physical form can be very complicated, and often unpredictable It is possible to produce a physical form that is partially amorphous and partially crys- talline The crystalline component could then be

Fig 9.8 The amorphous content induced in crystalline lactose

as a consequence of milling in an air-jet mill at different air pressures (Redrawn from Briggner et al 1994, with permission.)

Fig 9.9 The amorphous content of a model drug substance

following milling in a ball mill and a micronizer (Redrawn from Ahmed et al 1996, with permission.)

147

(a) crystalline lactose monohydrate, (b) amorphous lactose.

Đặc tính của tiểu phân chất rắn vận dụng trong bào chế

Rây đục lỗ

Xát hạt TD dính TD trơn

Độ hoà tan

Hấp thu

Độ

Ổn định

Hai giai đoạn: - Nghiền bột đơn

w   Đóng gói thuốc bột:

nước

Lọ đựng bột có nắp đục lỗ

PAPS (Laboratoires M RICHARD SA)

Một chai pha được

60 ml hỗn dịch; 5

ml hỗn dịch chứa

125 mg amoxicilin

và 31,25 mg acid clavulanic (tính qui đổi).

YÊU CẦU CHẤT LƯỢNG CỦA THUỐC BỘT

Tự đọc

w  Định nghĩa

hay sợi ngắn xốp

dung dịch, hỗn dịch…

THUỐC CỐM (GRANULES)